Prosthetic Heart Valves And Apparatus And Methods For Delivery Of Same

ABSTRACT

Apparatus and methods are described herein for various embodiments of a prosthetic heart valve, delivery apparatus and delivery methods for delivering a prosthetic heart valve to a heart of a patient via a transapical or transvascular delivery approach. In some embodiments, a prosthetic heart valve includes an outer frame coupled to an inner frame and the outer frame is movable between a first configuration relative to the inner frame and a second inverted configuration relative to the inner frame. The valve can be delivered to a heart using an apparatus that includes a delivery sheath that defines a lumen that can receive the prosthetic heart valve therein when the outer frame is in the inverted configuration. Actuation wires are releasably coupled to the outer frame and can be used to help revert the outer frame after the valve is deployed outside of the delivery sheath and within the heart.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/310,661, filed Dec. 17, 2018, which is a national phase entry under35 U.S.C. § 371 of International Application No. PCT/US2017/039972 filedJun. 29, 2017, published in English, which claims priority to and thebenefit of U.S. Provisional Application No. 62/356,828, filed Jun. 30,2016, entitled “Prosthetic Heart Valves and Apparatus and Methods forDelivery of Same,” the disclosures of which are all incorporated hereinby reference in their entireties.

BACKGROUND

Embodiments are described herein that relate to devices and methods foruse in the delivery and deployment of prosthetic valves, andparticularly to devices and methods for prosthetic heart valves thatprovide for delivery of the prosthetic heart valves to within a heart ofa patient in an inverted configuration.

Prosthetic heart valves can pose particular challenges for delivery anddeployment within a heart. Valvular heart disease, and specifically,aortic and mitral valve disease is a significant health issue in theUnited States (US); annually approximately 90,000 valve replacements areconducted in the US. Traditional valve replacement surgery involving theorthotopic replacement of a heart valve is considered an “open heart”surgical procedure. Briefly, the procedure necessitates surgical openingof the thorax, the initiation of extra-corporeal circulation with aheart-lung machine, stopping and opening the heart, excision andreplacement of the diseased valve, and re-starting of the heart. Whilevalve replacement surgery typically carries a 1-4% mortality risk inotherwise healthy persons, a significantly higher morbidity isassociated to the procedure largely due to the necessity forextra-corporeal circulation. Further, open heart surgery is often poorlytolerated in elderly patients. Thus elimination of the extra-corporealcomponent of the procedure could result in reduction in morbidities andcost of valve replacement therapies could be significantly reduced.

While replacement of the aortic valve in a transcatheter manner is thesubject of intense investigation, lesser attention has been focused onthe mitral valve. This is in part reflective of the greater level ofcomplexity associated to the native mitral valve apparatus, and thus, agreater level of difficulty with regards to inserting and anchoring thereplacement prosthesis. A need exists for delivery devices and methodsfor transcatheter mitral valve replacements.

Some known delivery methods include delivering a prosthetic mitral valvethrough an apical puncture site. In such a procedure, the valve isplaced in a compressed configuration within a lumen of a deliverycatheter of, for example, 34-36 Fr (i.e. an outer diameter of about11-12 mm). Delivery of a prosthetic valve to the atrium of the heart canbe accomplished, for example, via a transfemoral approach, transatriallydirectly into the left atrium of the heart, a jugular approach ortransapically. In many cases, it is desirable for the prosthetic valveto have a small outer perimeter or profile to allow insertion through asmaller delivery catheter of, for example, 28Fr (i.e. an outer diameterof about 9 mm).

Thus, a need exist for prosthetic heart valves that can have a smallprofile during delivery while still maintaining the size andcharacteristics needed to perform their desired function within theheart.

A need also exists for devices and methods for delivering and deployinga prosthetic heart valve within a heart, with the valve disposed withina small diameter delivery sheath and then moving the valve to anexpanded configuration within the heart.

SUMMARY

Apparatus and methods are described herein for various embodiments of aprosthetic heart valve, delivery apparatus and delivery methods fordelivering a prosthetic heart valve to a heart of a patient via atransvascular and a transapical delivery approach. In some embodiments,a prosthetic heart valve includes an outer frame coupled to an innerframe and the outer frame is movable between a first configurationrelative to the inner frame and a second inverted configuration relativeto the inner frame. The valve can be delivered to a heart using anapparatus that includes a delivery sheath that defines a lumen that canreceive the prosthetic heart valve therein when the outer frame is inthe inverted configuration. Actuation wires are releasably coupled tothe outer frame and can be used to help revert the outer frame after thevalve is deployed outside of the delivery sheath and within the heart.

BRIEF DESCRIPTION OF THE FIGURES

FIGS. 1A and 1B are schematic illustrations of a portion of a prostheticheart valve, according to an embodiment, shown in a first configurationand a second configuration, respectively.

FIGS. 1C and 1D are schematic illustrations of the portion of theprosthetic heart valve of FIGS. 1A and 1B, respectively, shown disposedwithin a delivery sheath.

FIGS. 2A and 2B are schematic illustrations of the portion of aprosthetic heart valve of FIGS. 1A and 1B, shown in the firstconfiguration and the second configuration, respectively.

FIGS. 3-5 are front, bottom, and top views of a prosthetic heart valveaccording to an embodiment.

FIG. 6 is an opened and flattened view of the inner frame of theprosthetic heart valve of FIGS. 3-5, in an unexpanded configuration.

FIGS. 7 and 8 are side and bottom views, respectively, of the innerframe of FIG. 6 in an expanded configuration.

FIG. 9 is an opened and flattened view of the outer frame of the valveof FIGS. 3-5, in an unexpanded configuration.

FIGS. 10 and 11 are side and top views, respectively, of the outer frameof FIG. 9 in an expanded configuration.

FIGS. 12-14 are side, front, and top views of an assembly of the innerframe of FIGS. 6-8 and the outer frame of FIGS. 9-11.

FIG. 15 is a side perspective view of an assembly of an inner frame andan outer frame shown in a biased expanded configuration, according to anembodiment.

FIG. 16 is a side perspective view of the assembly of FIG. 15 with theouter frame shown inverted.

FIG. 17 is side view of the assembly of FIG. 16 shown in a collapsedconfiguration within a lumen of a delivery sheath.

FIG. 18 is a side view of the assembly of FIG. 17 shown in a firstpartially deployed configuration.

FIG. 19 is a side view of the assembly of FIG. 17 shown in a secondpartially deployed configuration.

FIG. 20 is a side view of the assembly of FIG. 17 shown in a thirdpartially deployed configuration in which the inverted outer frame issubstantially deployed outside of the delivery sheath.

FIG. 21 is a side view of the assembly of FIG. 17 shown in a fourthpartially deployed configuration in which the outer frame has revertedand assumed a biased expanded configuration.

FIGS. 22-24 illustrate steps of a portion of a method to deliver theprosthetic valve of FIGS. 15-21 to an atrium of a heart and within thenative mitral annulus.

FIG. 25 is a schematic illustration of a delivery device and prostheticheart valve, according to an embodiment.

FIG. 26A is a side view of a portion of the prosthetic heart valve ofFIG. 25 shown within a delivery sheath and coupled to a valve holder.

FIG. 26B is a side view of an attachment member of the prosthetic valveof FIG. 26A.

FIG. 26C is an end view of the valve holder of FIG. 26A.

FIG. 27 is a cross-sectional side view of a prosthetic valve in aninverted configuration inside of a delivery sheath, according to anembodiment.

FIG. 28 is a portion of a cross-sectional side view of a prostheticvalve in an inverted configuration inside of a delivery sheath,including a dilator, according to an embodiment.

FIG. 29A is a cross-sectional side view of a prosthetic heart valve inan inverted configuration inside a lumen of a delivery sheath, accordingto an embodiment.

FIG. 29B is a side view of the prosthetic heart valve of FIG. 9A in areverted configuration and outside the delivery sheath.

FIGS. 30A and 30B are schematic illustrations of a portion of aprosthetic heart valve, according to an embodiment, shown in a firstconfiguration and a second configuration, respectively.

FIGS. 30C and 30D are schematic illustrations of the portion of theprosthetic heart valve of FIGS. 30A and 30B, respectively, showndisposed within a delivery sheath.

FIGS. 31A and 31B are schematic illustrations of the portion of aprosthetic heart valve of FIGS. 30A and 30B, shown in the firstconfiguration and the second configuration, respectively.

FIG. 32A is schematic illustration in side view of a delivery device andprosthetic heart valve, according to an embodiment.

FIG. 32B is a schematic illustration of an end view of an elongatemember of the delivery device of FIG. 32A.

FIG. 33A is a cross-sectional side-view of a delivery sheath, with aprosthetic valve in an inverted configuration and disposed therein,according to an embodiment.

FIG. 33B is an illustration in side view of the prosthetic heart valveof FIG. 33A in a reverted configuration and outside the delivery sheath.

FIG. 33C is an illustration of an end view of the elongate member of thedelivery device of FIG. 33A.

FIG. 33D is an illustration of an end view of an elongate member of adelivery device, according to an embodiment.

FIG. 34 is a partial cross-sectional side view of a delivery system andprosthetic heart valve, according to an embodiment.

FIG. 35 is a cross-sectional view taken along line 35-35 in FIG. 34showing the actuation wires coupled to a tube member of the deliverysystem.

FIG. 36 is a proximal end view of a tube member of the delivery systemof FIG. 34.

FIG. 37A is a side view of a portion of the tube member of FIG. 36.

FIG. 37B is a side view of a portion of a multi-lumen tube memberaccording to another embodiment and a distal retention element accordingto an embodiment.

FIG. 37C view of a portion of the multi-lumen tube member of FIG. 37Band a distal retention element, according to another embodiment.

FIGS. 38A-38D are each a side view of a different embodiment of anactuation wire.

FIG. 39 is a partial cross-sectional side view of the delivery systemand prosthetic heart valve of FIG. 34, shown in a first partiallydeployed configuration.

FIG. 40 is a partial cross-sectional side view of the delivery systemand prosthetic heart valve of FIG. 34, shown in a second partiallydeployed configuration.

FIG. 41 is a partial cross-sectional side view of the delivery systemand prosthetic heart valve of FIG. 34, shown in a third partiallydeployed configuration.

FIG. 42 is a cross-sectional view taken along line A-A in FIG. 34showing the actuation wires in a partially released position.

FIG. 43 is a flowchart illustrating a method of delivering and deployinga prosthetic valve within a heart, according to an embodiment.

FIG. 44 is a flowchart illustrating a method of delivering and deployinga prosthetic valve within a heart, according to an embodiment.

DETAILED DESCRIPTION

Apparatus and methods are described herein for prosthetic heart valves,such as prosthetic mitral valves, that can be configured to be moved toan inverted configuration for delivery of the prosthetic valve to withina heart of a patient. As described herein, in some embodiments, aprosthetic valve includes an outer frame that can be inverted relativeto an inner frame when the prosthetic valve is in a biased expandedconfiguration. The prosthetic mitral valve can be formed with, forexample, a shape-memory material. After inverting the outer frame, theprosthetic valve can be inserted into a lumen of a delivery sheath suchthat the prosthetic valve is moved to a collapsed configuration.

The delivery sheath can be used to deliver the prosthetic valve towithin a patient's heart using a variety of different deliveryapproaches for delivering a prosthetic heart valve (e.g., prostheticmitral valve) where the inverted prosthetic valve would enter the heartthrough the atrium of the heart. For example, the prosthetic valvesdescribed herein can be delivered using a transfemoral delivery approachas described in PCT International Application No. PCT/US15/14572 (the“572 PCT application”) and/or in PCT International Application No.PCT/US16/12305 (the “'305 PCT Application”), each disclosure of which isincorporated by reference in its entirety herein, or via a transatrialapproach, such as described in U.S. Provisional Patent Application Ser.No. 62/220,704, entitled “Apparatus and Methods for Transatrial Deliveryof Prosthetic Mitral Valve,” filed Sep. 18, 2015 (the “'704 provisionalapplication”), which is incorporated herein by reference in itsentirety. In another example, the prosthetic valves described herein(e.g., an inverted valve as described herein) could be delivered via atransjugular approach, e.g., via the right atrium and through the atrialseptum and into the left atrium, as described in U.S. Provisional PatentApplication Ser. No. 62/305,678, entitled “Apparatus and Methods forDelivery of Prosthetic Mitral Valve,” (the “'678 provisionalapplication”) and in U.S. Patent Application Pub. No. 2017/0079790,entitled “Apparatus and Methods for Delivery of Prosthetic MitralValve,” (the “'790 publication”) each incorporated by reference in itsentirety herein. The prosthetic valves described herein can also bedelivered apically if desired. With a transapical approach, after thedelivery sheath has been disposed within the left atrium of the heart,the prosthetic mitral valve is moved distally out of the delivery sheathsuch that the inverted outer frame reverts and the prosthetic valveassumes its biased expanded configuration. The prosthetic mitral valvecan then be positioned within a mitral annulus of the heart.

In some embodiments, an apparatus includes a delivery sheath thatdefines a lumen, an elongate member that defines a first lumen and asecond lumen and is at least partially disposed within the lumen of thedelivery sheath. The apparatus further includes a prosthetic heart valvedisposed at least partially within the lumen of the delivery sheath in acollapsed configuration and circumferentially about a portion of theelongate member. The prosthetic heart valve includes an outer framecoupled to an inner frame. The outer frame is movable between a firstconfiguration relative to the inner frame and a second configurationrelative to the inner frame in which the outer frame is invertedrelative to the inner frame. The prosthetic heart valve is disposedwithin the lumen of the delivery sheath with the outer frame in thesecond configuration and disposed axially proximal to the inner frame.The apparatus further includes a first actuation wire releasably coupledto a first portion of the outer frame and routed from the first portionthrough the first lumen of the elongate member and out a proximal endportion of the delivery sheath. The apparatus further includes a secondactuation wire releasably coupled to a second portion of the outer frameand routed from the second portion through the second lumen of theelongate member and out the proximal end portion of the delivery sheath.The first portion and the second portion of the outer frame areconfigured to be disposed within an atrium of a heart when implantedwithin the heart.

In some embodiments, a method includes inserting a distal end portion ofa delivery sheath through an apical region of a heart and into an atriumof the heart. The delivery sheath has a prosthetic heart valve disposedwithin a lumen of the delivery sheath. The prosthetic heart valveincludes an outer frame and an inner frame coupled to the outer frame.The outer frame is movable between a first position relative to theinner frame and a second position relative to the inner frame in whichthe outer frame is inverted relative to the inner frame. The prostheticheart valve is disposed within the lumen of the delivery sheath with theouter frame in the second position relative to the inner frame duringthe inserting. The method further includes moving the prosthetic heartvalve distally out of the delivery sheath. The method further includescausing the outer frame of the prosthetic heart valve to transition tothe first position relative to the inner frame such that the prostheticheart valve at least partially assumes a biased expanded configuration.The method further includes positioning the prosthetic heart valvewithin an annulus of the heart.

In some embodiments, a method includes inserting a distal end portion ofa delivery sheath into an atrium of a heart. The delivery sheath has aprosthetic heart valve disposed within a lumen of the delivery sheath.The prosthetic heart valve includes an outer frame and an inner framecoupled to the outer frame. The outer frame is movable between a firstposition relative to the inner frame and a second position relative tothe inner frame in which the outer frame is inverted relative to theinner frame. The prosthetic heart valve is disposed within the lumen ofthe delivery sheath with the outer frame in the second position relativeto the inner frame and disposed at least partially axially proximal tothe inner frame during the inserting. The method further includes movingthe prosthetic heart valve distally out of the delivery sheath. Themethod further includes causing the outer frame of the prosthetic heartvalve to transition to the first position relative to the inner framesuch that the prosthetic heart valve at least partially assumes a biasedexpanded configuration. The method further includes positioning theprosthetic heart valve within an annulus of the heart.

In some embodiments, an apparatus includes an outer sheath that definesa lumen, a delivery sheath that defines a lumen and is movably disposedwithin the lumen defined by the outer sheath, and a prosthetic heartvalve disposed within the lumen of the delivery sheath in a collapsedconfiguration. The prosthetic heart valve includes an outer framecoupled to an inner frame. The inner frame is removably coupled to adistal end portion of a valve holder. The outer frame is movable betweena first configuration relative to the inner frame and a secondconfiguration relative to the inner frame in which the outer frame isinverted relative to the inner frame. The prosthetic heart valve isdisposed within the lumen of the delivery sheath with the outer frame inthe second configuration. The apparatus further includes a firstactuation wire releasably copuled to a first portion of the outer frame,and a second acutation wire releasably coupled to a second portion ofthe outer frame. Each of the first acutation wire and the secondacutation wire has (1) a first portion extending proximally from theouter frame, through the lumen of the outer sheath, along an outsidewall of the delivery sheaht, and through a first side aperture definedby the delivery sheath, and (2) a second portion extending proximallyfrom the outer frame, through the lumen of the outer sheaht, along theoutside all of the delivery sheaht, and through a second side aperturedefined by the delivery sheath. The first portion and the second portionof each of the first acutation wire and the second acutation wire areconfigured to be pulled proximally to urge the outer frame from thesecond configuration towards the first configuration relative to theinner frame.

In some embodiments, an apparatus includes a prosthetic valve thatincludes an inner frame and an outer frame coupled to the inner frame atmultiple coupling joints. The multiple coupling joints are configured toallow the outer frame to be moved relative to inner frame such that theprosthetic valve can be moved between a first configuration and a secondconfiguration. The outer frame and the inner frame collectively define afirst length of the prosthetic valve when the prosthetic valve is in thefirst configuration and a second length of the prosthetic valve when theprosthetic valve is in the second configuration and the second length isgreater than the first length. The inner frame has a length that is thesame when the prosthetic valve is in both the first configuration andthe second configuration.

In some embodiments, an apparatus includes a prosthetic heart valve thatincludes an inner frame and an outer frame coupled to the inner frame atmultiple coupling joints. The prosthetic valve is movable between afirst configuration and a second configuration. The multiple couplingjoints are configured to allow the outer frame to be moved between afirst position relative to the inner frame and a second positionrelative to inner frame in which the outer frame is inverted relative tothe inner frame. The prosthetic valve is in the first configuration whenthe outer frame is in the first position, and in the secondconfiguration when the outer frame is in the second position.

In some embodiments, an apparatus includes a prosthetic heart valve thatincludes an inner frame, and an outer frame coupled to the inner frameat multiple coupling joints. The multiple coupling joints are configuredto allow the outer frame to be moved relative to inner frame such thatthe prosthetic valve can be moved between a first configuration and asecond configuration. The outer frame has an outer frame couplingportion coupled to the inner frame at multiple coupling joints and anouter frame free end portion. The inner frame has an inner framecoupling portion coupled to the outer frame at the multiple couplingjoints. A first end portion and an inner frame free end portion are onan opposite end of the inner frame from the first end portion. Themultiple coupling joints are disposed between the outer frame free endportion and the first end portion of the inner frame when the prostheticvalve is in the first configuration. The multiple coupling joints aredisposed between the inner frame free end portion and the outer framefree end portion when the prosthetic valve is in the secondconfiguration.

In some embodiments, an apparatus includes a prosthetic heart valve thatincludes an inner frame coupled to an outer frame at multiple couplingjoints. The multiple coupling joints are configured to allow the outerframe to be moved relative to inner frame such that the prosthetic valvecan be moved between a first configuration and a second configuration.The outer frame has an outer frame coupling portion coupled to the innerframe at the multiple coupling joints and an outer frame free endportion. The inner frame has an inner frame coupling portion coupled tothe outer frame at the multiple coupling joints and an inner frame freeend portion. The outer frame free end portion and the inner frame freeend portion each open in the same direction when the prosthetic valve isin the first configuration. The outer frame free end portion and theinner frame free end portion open in opposite directions when theprosthetic valve is in the second configuration.

In some embodiments, an apparatus includes a delivery sheath thatdefines a lumen, a valve holder movably disposable within the lumen ofthe delivery sheath and a prosthetic heart valve disposed at leastpartially within the lumen of the delivery sheath in a collapsedconfiguration. The prosthetic heart valve includes an outer framecoupled to an inner frame and the inner frame is removably coupled to adistal end portion of the valve holder. The outer frame is movablebetween a first configuration relative to the inner frame and a secondconfiguration relative to the inner frame in which the outer frame isinverted relative to the inner frame. The prosthetic heart valve isdisposed within the lumen of the delivery sheath with the outer frame inthe second configuration. A first actuation wire is releasably coupledto a first portion of an open free end portion of the outer frame and asecond actuation wire is releasably coupled to a second portion of theopen free end portion of the outer frame. Each of the first actuationwire and the second actuation wire have a first portion extendingproximally from the outer frame and a second portion extendingproximally from the outer frame. The first portion and the secondportion of each of the first actuation wire and the second actuationwire are configured to be pulled proximally to urge the outer frame fromthe second configuration towards the first configuration relative to theinner frame.

In some embodiments, an apparatus includes an outer sheath that definesa lumen, an inner sheath movably disposed within the lumen of the outersheath and defining a lumen, a tube member movably disposed within thelumen of the outer sheath and defining a lumen, a valve holder movablydisposed within the lumen of the inner sheath and within a lumen definedby the tube member and a prosthetic heart valve disposed at leastpartially within the lumen of the outer sheath and at least partiallywithin the lumen of the inner sheath. The prosthetic heart valveincludes an outer frame coupled to an inner frame and the inner frame isremovably coupled to a distal end portion of the valve holder. The outerframe is movable between a first configuration relative to the innerframe and a second configuration relative to the inner frame in whichthe outer frame is inverted relative to the inner frame. The prostheticheart valve is disposed within the lumen of the outer sheath and thelumen of the inner sheath with the outer frame in the secondconfiguration. A first actuation wire is releasably coupled to a firstportion of an open free end portion of the outer frame and releasablycoupled to the tube member at a first location on the tube member. Asecond actuation wire is releasably coupled to a second portion of theopen free end portion of the outer frame and releasably coupled to thetube member at a second location on the tube member.

In some embodiments, a method includes inserting a distal end portion ofa delivery sheath into a left atrium of a heart. The delivery sheathhaving a prosthetic mitral valve disposed within a lumen of the deliverysheath and the prosthetic mitral valve has an outer frame coupled to aninner frame such that the outer frame can be moved between a firstposition relative to the inner frame and a second position relative tothe inner frame in which the outer frame is inverted relative to theinner frame. The prosthetic valve is disposed within the lumen of thedelivery sheath with the outer frame in the second positon relative tothe inner frame. The prosthetic mitral valve is moved distally out ofthe delivery sheath causing the outer frame of the prosthetic mitralvalve to revert back to the first position relative to the inner framesuch that the prosthetic mitral valve at least partially assumes abiased expanded configuration. The prosthetic mitral valve is positionedwithin a mitral annulus of the heart.

FIGS. 1A and 1B are schematic illustrations of a portion of a prostheticheart valve 100, according to an embodiment, shown in a firstconfiguration and a second configuration respectively, and FIGS. 1C and1D illustrate the portions of the prosthetic heart valve 100 of FIGS. 1Aand 1B, respectively, shown disposed within a lumen of a delivery sheath126. FIGS. 2A and 2B illustrate a portion of the prosthetic heart valve100 of FIGS. 1A and 1B, respectively, and show length dimensions for theprosthetic heart valve in each of the first configuration and the secondconfiguration. As described above, in some situations, such as whendelivering a prosthetic valve to the heart via a transfemoral,transatrial or transjugular approach, because of the smaller size of thelumen of the delivery sheath, the size of the prosthetic valve duringdelivery should be sized accordingly. Thus, it is desirable to have aprosthetic valve that can be reconfigured between a biased expandedconfiguration for implantation in the heart (e.g., within a nativemitral annulus) and a delivery configuration that has a smaller outerperimeter or profile to allow for delivery within the lumen of thedelivery sheath. The prosthetic valve 100 and the embodiments of aprosthetic valve described herein can be constructed and formed toachieve these desired functions and characteristics.

The prosthetic heart valve 100 (also referred to herein as “prostheticvalve” or “valve”) can be, for example, a prosthetic mitral valve. Thevalve 100 includes an outer frame 120 and an inner frame 150. The outerframe 120 and the inner frame 150 are each formed as a tubular structureas described in more detail below with reference to FIGS. 3-15. Theouter frame 120 and the inner frame 150 can be coupled together atmultiple coupling joints 146 disposed about a perimeter of the innerframe 150 and a perimeter of the outer frame 120 as described in moredetail below. The valve 100 can also include other features, such asthose described with respect to FIGS. 3-15 below. For illustrationpurposes, only the inner frame 150 and the outer frame 120 are discussedwith respect to FIGS. 1A-2B. The various characteristics and features ofvalve 100 described with respect to FIGS. 1A-2B can apply to any of theprosthetic valves described here.

The outer frame 120 is configured to have a biased expanded orundeformed shape and can be manipulated and/or deformed (e.g.,compressed or constrained) and, when released, return to its original(expanded or undeformed) shape. For example, the outer frame 120 can beformed of materials, such as metals or plastics, which have shape memoryproperties. With regards to metals, Nitinol® has been found to beespecially useful since it can be processed to be austenitic,martensitic or super elastic. Other shape memory alloys, such asCu—Zn—Al—Ni alloys, and Cu—Al—Ni alloys, may also be used. The innerframe 150 can be formed from a laser-cut tube of Nitinol®. The innerframe 150 can also have a biased expanded or undeformed shape and can bemanipulated and/or deformed (e.g., compressed and/or constrained) and,when released, return to its original (expanded or undeformed) shape.Further details regarding the inner frame 150 and the outer frame 120are described below with respect to valve 200 and FIGS. 3-15.

The valve 100 can be delivered and deployed within a left atrium of aheart using a variety of different delivery approaches including, forexample, a transfemoral delivery approach, as described in the '572 PCTapplication and/or in the '305 PCT application, or a transatrial ortransjugular approach, as described in the '704 provisional application,the '678 provisional application and the '790 publication”) incorporatedby reference above. As described above, in some situations, such as whendelivering a prosthetic valve to the heart via a transfemoral ortransatrial approach, because of the smaller size of the lumen of thedelivery sheath, the size of the prosthetic valve during delivery shouldbe sized accordingly. Thus, it is desirable to have a prosthetic valvethat can be reconfigured between a biased expanded configuration forimplantation in the heart (e.g., within a native mitral annulus) and adelivery configuration that has a smaller outer perimeter or profile toallow for delivery within the lumen of the delivery sheath. Theprosthetic valve 100 and the embodiments of a prosthetic valve describedherein can be constructed and formed to achieve these desired functionsand characteristics.

More specifically, the valve 100 can have a biased expandedconfiguration (as shown in FIGS. 1A and 2A), an inverted configuration(as shown in FIGS. 1B and 2B), and a compressed or collapsedconfiguration (as shown in FIGS. 1C and 1D). The expanded configurationallows the valve 100 to function when implanted within the heart. Thevalve 100 can be moved to the inverted configuration and the compressedor collapsed configuration for delivery of the valve 100 to the heart ofa patient.

To enable the valve 100 to be moved to the inverted configuration, theouter frame 120 can be coupled to the inner frame 150 in such a mannerto allow the outer frame 120 to move relative to the inner frame 150.More specifically, the coupling joints 146 can couple the outer frame120 to the inner frame 150 in such a manner to allow the outer frame 120to be moved relative to the inner frame 150. For example, in someembodiments, the coupling joints 146 can be configured to allow theouter frame 120 to rotate about the coupling joint 146 relative to theinner frame 150. In some embodiments, coupling joints can provide apivotal coupling between the outer frame 120 and the inner frame 150. Insome embodiments, the coupling joints can provide a flexible attachmentbetween the outer frame 120 and the inner frame 150. The coupling joints146 can be a variety of different types and configurations as describedherein with reference to the various embodiments of a prosthetic valve.For example, the coupling joints 146 can include a living hinge, aflexible member, sutures, a suture wrapped through an opening, a pin ortab inserted through an opening or any combinations thereof.

To move the valve 100 from the expanded configuration (FIG. 1A) to theinverted configuration (FIG. 1B), the outer frame 120 is moved to aprolapsed or inverted configuration relative to the inner frame 150, asshown in FIGS. 1B, 1D and 2B, by moving (e.g., rotating, pivoting,flexing) the outer frame 120 about the coupling joints 146. The elasticor superelastic structure of outer frame 120 of valve 100 also allowsthe outer frame 120 to be moved to, and disposed in, the prolapsed orinverted configuration relative to the inner frame 150. To move theouter frame 120 to the inverted configuration relative to the innerframe 150, the outer frame 120 is folded or inverted distally (to theright in FIG. 1B) relative to the inner frame 150 via the couplingjoints 146. As shown in FIGS. 1A and 2A, the outer frame 120 is in afirst position relative to the inner frame 150 prior to being invertedin which an open or free end portion 116 (also referred to the atriumportion 116 of the outer frame 120) is disposed proximally or to theleft of the coupling joints 146 and in the same direction as a free endportion 147 (also referred to as a second end portion of the innerframe) of the inner frame 150. When the outer frame 120 is moved to aninverted configuration (i.e., second positon relative to the inner frame150), the free end portion 116 is disposed distally of the couplingjoints 146 (or to the right in FIGS. 1B and 2B) and in an oppositedirection as the free end portion 147 of the inner frame 150. Saidanother way, when the valve 100 is in a biased expanded configuration(e.g., FIG. 1A), the coupling joints 146 are disposed between a firstend portion 144 (also referred to as a tether coupling portion) of theinner frame 150 and the free end portion 116 of the outer frame 120.When the valve 100 is in the inverted configuration (e.g., FIG. 1B)(i.e., the outer frame 120 has been moved to an inverted configurationor position), the coupling joints 146 are disposed between the free endportion or second end portion 147 of the inner frame 150 and the freeend portion 116 of the outer frame 120.

When in the inverted configuration, an overall length of the valve 100is increased, but a length of the inner frame 150 and a length of theouter frame 120 remains the same (or substantially the same). Forexample, as shown in FIGS. 2A and 2B an overall length L1 of the valve100 in the biased expanded configuration (prior to being inverted asshown in FIG. 2A) is less than the overall length L2 of the valve 100when in the inverted configuration (FIG. 2B). A length Li of the innerframe 150 and a length Lo of the outer frame 120 is substantially thesame (or the same) when the valve 100 is in both the biased expandedconfiguration and the inverted configuration. In addition, in someinstances, depending on the specific configuration of the outer frame,an overall outer perimeter or outer diameter of the valve 100 can besmaller when the valve 100 is in the inverted configuration.

With the valve 100 in the inverted configuration, the valve 100 can beplaced within a lumen of the delivery sheath 126 for delivery of thevalve 100 to the left atrium of the heart, as shown in FIG. 1D. Whenplaced within the lumen of the delivery sheath 126, the valve 100 ismoved to the collapsed or compressed configuration in which the outerdiameter or outer perimeter of the valve 100 is reduced. Because thevalve 100 is in the inverted configuration, the valve 100 is able to beplaced within a smaller delivery sheath 126 than would otherwise bepossible. For example, for comparison purposes, FIG. 1C illustrates thevalve 100 placed within a lumen of a delivery sheath 126′ where thevalve 100 has not been moved to an inverted configuration prior to beingdisposed within the delivery sheath 126′. As shown in FIG. 1C, an outerdiameter of the valve 100 is reduced, but not to as small of a diameteras for the valve 100 when placed in a delivery sheath 126 when in theinverted configuration. Thus, in FIG. 1C, the valve 100 has an overallouter perimeter or outer diameter D1 and in FIG. 1D, the valve 100 hasan overall outer perimeter or outer diameter D2, which is less than D1.

Thus, by disposing the outer frame 120 in the inverted configuration,the valve 100 can be collapsed into a smaller overall diameter, i.e.placed in a smaller diameter delivery sheath 126, than would be possibleif the valve 100 were merely collapsed radially. This is because whenthe valve is in the biased expanded configuration, the inner frame 150is nested within an interior of the outer frame 120, and thus the outerframe 120 must be collapsed around the inner frame 150. In someembodiments, the inner frame 150 and the outer frame are disposedconcentrically. Whereas in the inverted configuration, the inner frame150 and the outer frame 120 are arranged axially with respect to eachother (i.e., the inner frame is not nested within the outer frame 150),such that the outer frame 120 can be collapsed without needing toaccommodate all of the structure of the inner frame 150 inside it. Inother words, with the inner frame 150 disposed mostly inside or nestedwithin the outer frame 120, the layers or bulk of the frame structurescannot be compressed to as small a diameter. In addition, if the framesare nested, the structure is less flexible, and therefore, more force isneeded to bend the valve, e.g. to pass through tortuous vasculature orto make tight turn in the left atrium after passing through the atrialseptum to be properly oriented for insertion into the mitral valveannulus.

FIGS. 3-14 illustrate another embodiment of a prosthetic heart valvethat can be delivered and deployed within a left atrium of a heart usinga variety of different delivery approaches including, for example, atransfemoral delivery approach or a transatrial delivery approach. FIGS.3-5 are front, bottom, and top views, respectively, of a prostheticheart valve 200 according to an embodiment. Prosthetic heart valve 200(also referred to herein as “valve” or “prosthetic valve”) is designedto replace a damaged or diseased native heart valve such as a mitralvalve. Valve 200 includes an outer frame assembly 210 and an inner valveassembly 240 coupled to the outer frame assembly 210.

As shown, outer frame assembly 210 includes an outer frame 220, coveredon all or a portion of its outer face with an outer covering 230, andcovered on all or a portion of its inner face by an inner covering 232.Outer frame 220 can provide several functions for prosthetic heart valve200, including serving as the primary structure, as an anchoringmechanism and/or an attachment point for a separate anchoring mechanismto anchor the valve to the native heart valve apparatus, a support tocarry inner valve assembly 240, and/or a seal to inhibit paravalvularleakage between prosthetic heart valve 200 and the native heart valveapparatus.

Outer frame 220 has a biased expanded configuration and can bemanipulated and/or deformed (e.g., compressed and/or constrained) and,when released, return to its original unconstrained shape. To achievethis, outer frame 220 can be formed of materials, such as metals orplastics, which have shape memory properties. With regards to metals,Nitinol® has been found to be especially useful since it can beprocessed to be austenitic, martensitic or super elastic. Other shapememory alloys, such as Cu—Zn—Al—Ni alloys, and Cu—Al—Ni alloys, may alsobe used.

As best shown in FIG. 3, outer frame assembly 210 has an upper end(e.g., at the atrium portion 216), a lower end (e.g., at the ventricleportion 212), and a medial portion (e.g., at the annulus portion 214)therebetween. The upper end or atrium portion 216 (also referred to as“outer free end portion”) defines an open end portion of the outer frameassembly 210. The medial or annulus portion 214 of the outer frameassembly 210 has a perimeter that is configured (e.g., sized, shaped) tofit into an annulus of a native atrioventricular valve. The upper end ofthe outer frame assembly 210 has a perimeter that is larger than theperimeter of the medial portion. In some embodiments, the perimeter ofthe upper end of the outer frame assembly 210 has a perimeter that issubstantially larger than the perimeter of the medial portion. As shownbest in FIG. 5, the upper end and the medial portion of the outer frameassembly 210 has a D-shaped cross-section. In this manner, the outerframe assembly 210 promotes a suitable fit into the annulus of thenative atrioventricular valve.

Inner valve assembly 240 includes an inner frame 250, an outer covering(not shown), and leaflets 270. As shown, the inner valve assembly 240includes an upper portion having a periphery formed with multiplearches. The inner frame 250 includes six axial posts or frame membersthat support the outer covering of the inner valve assembly 240 andleaflets 270. Leaflets 270 are attached along three of the posts, shownas commissure posts 252 (best illustrated in FIG. 4), and the outercovering of the inner valve assembly 240 is attached to the other threeposts, 254 (best illustrated in FIG. 4), and optionally to commissureposts 252. Each of outer covering of the inner valve assembly 240 andleaflets 270 are formed of approximately rectangular sheets of material,which are joined together at their upper, or atrium end. The lower,ventricle end of the outer covering of the inner valve assembly 240 maybe joined to inner covering 232 of outer frame assembly 210, and thelower, ventricle end of leaflets 270 may form free edges 275, thoughcoupled to the lower ends of commissure posts 252.

Although inner valve assembly 240 is shown as having three leaflets, inother embodiments, an inner valve assembly can include any suitablenumber of leaflets. The leaflets 270 are movable between an openconfiguration and a closed configuration in which the leaflets 270coapt, or meet in a sealing abutment.

Outer covering 230 of the outer frame assembly 210 and inner covering232 of outer frame assembly 210, outer covering 260 of the inner valveassembly 240 and leaflets 270 of the inner valve assembly 240 may beformed of any suitable material, or combination of materials, such asthose discussed above. In this embodiment, the inner covering 232 of theouter frame assembly 210, the outer covering of the inner valve assembly240, and the leaflets 270 of the inner valve assembly 240 are formed, atleast in part, of porcine pericardium. Moreover, in this embodiment, theouter covering 230 of the outer frame assembly 210 is formed, at leastin part, of polyester.

Inner frame 250 is shown in more detail in FIGS. 6-8. Specifically,FIGS. 6-8 show inner frame 250 in an undeformed, initial state (FIG. 6),a side view of the inner frame 250 in an expanded configuration (FIG.7), and a bottom view of the inner frame 250 in the expandedconfiguration (FIG. 8), respectively, according to an embodiment.

In this embodiment, inner frame 250 is formed from a laser-cut tube ofNitinol®. Inner frame 250 is illustrated in FIG. 6 in an undeformed,initial state, i.e. as laser-cut, but cut and unrolled into a flat sheetfor ease of illustration. Inner frame 250 can be divided into fourportions, corresponding to functionally different portions of the innerframe 250 in final form: atrial portion 247, body portion 242, strutportion 243, and tether clamp or connecting portion 244. Strut portion243 includes six struts, such as strut 243A, which connect body portion242 to tether connecting portion 244.

Tether connecting portion 244 (also referred to as first end portion ofinner frame) includes longitudinal extensions of the struts, connectedcircumferentially by pairs of opposed, slightly V-shaped connectingmembers (or “micro-Vs”). Tether connecting portion 244 is configured tobe radially collapsed by application of a compressive force, whichcauses the micro-Vs to become more deeply V-shaped, with the verticesmoving closer together longitudinally and the open ends of the V shapesmoving closer together circumferentially. Thus, tether connectingportion 244 can be configured to compressively clamp or grip one end ofa tether, either connecting directly onto a tether line (e.g. braidedfilament line) or onto an intermediate structure, such as a polymer ormetal piece that is in term firmly fixed to the tether line.

In contrast to tether connecting portion 244, atrial portion 247 (alsoreferred to as “inner frame free end portion”) and body portion 242 areconfigured to be expanded radially. Strut portion 243 forms alongitudinal connection and radial transition between the expanded bodyportion and the compressed tether connecting portion 244. Body portion242 provides an inner frame coupling portion 245 that includes sixlongitudinal posts, such as post 242A. The inner frame coupling portion245 can be used to attach leaflets 270 to inner frame 240, and/or can beused to attach inner assembly 240 to outer assembly 210, such as byconnecting inner frame 250 to outer frame 220. In the illustratedembodiment, the posts include openings through which connecting members(such as suture filaments and/or wires) can be passed to couple theposts to other structures.

Inner frame 250 is shown in a fully deformed, i.e. the final, deployedconfiguration, in side view and bottom view in FIGS. 7 and 8,respectively.

Outer frame 220 of valve 200 is shown in more detail in FIGS. 9-11. Inthis embodiment, outer frame 220 is also formed from a laser-cut tube ofNitinol®. Outer frame 220 is illustrated in FIG. 9 in an undeformed,initial state, i.e. as laser-cut, but cut and unrolled into a flat sheetfor ease of illustration. Outer frame 220 can be divided into an outerframe coupling portion 271, a body portion 272, and a cuff portion 273(which includes the atrium or free end portion 216), as shown in FIG. 9.Outer frame coupling portion 271 includes multiple openings orapertures, such as 271A, by which outer frame 220 can be coupled toinner frame 250, as discussed in more detail below.

Outer frame 220 is shown in a fully deformed, i.e. the final, deployedconfiguration, in side view and top view in FIGS. 10 and 11,respectively. As best seen in FIG. 11, the lower end of outer framecoupling portion 271 forms a roughly circular opening (identified by “O”in FIG. 11). The diameter of this opening preferably correspondsapproximately to the diameter of body portion 242 of inner frame 250, tofacilitate coupling of the two components of valve 200.

Outer frame 220 and inner frame 250 are shown coupled together in FIGS.12-14, in front, side, and top views, respectively. The two framescollectively form a structural support for a prosthetic valve such asvalve 200. The frames support the valve leaflet structure (e.g.,leaflets 270) in the desired relationship to the native valve annulus,support the coverings (e.g., outer covering 230, inner covering 232,outer covering of inner valve assembly 240) for the two frames toprovide a barrier to blood leakage between the atrium and ventricle, andcouple to the tether (e.g., tether assembly 290) (by the inner frame250) to aid in holding the prosthetic valve 200 in place in the nativevalve annulus by the tether connection to the ventricle wall. The outerframe 220 and the inner frame 250 are connected at six coupling points(representative points are identified as “C”). In this embodiment, thecoupling points are implemented with a mechanical fastener, such as ashort length of wire, passed through an aperture (such as aperture 271A)in outer frame coupling portion 271 and corresponding openings in innerframe coupling portion 245 (e.g., longitudinal posts, such as post 242A)in body portion 242 of inner frame 250. Inner frame 250 is thus disposedwithin the outer frame 220 and securely coupled to it.

FIGS. 15-21 illustrate a method of reconfiguring a prosthetic heartvalve 300 (e.g., prosthetic mitral valve) prior to inserting theprosthetic heart valve 300 into a delivery sheath 326 (see, e.g., FIGS.17-21) for delivery into the atrium of the heart. The prosthetic heartvalve 300 (also referred to herein as “valve”) can be constructed thesame as or similar to, and function the same as or similar to the valves100 and 200 described above. Thus, some details regarding the valve 300are not described below. It should be understood that for features andfunctions not specifically discussed, those features and functions canbe the same as or similar to the valve 200.

As shown in FIG. 15, the valve 300 has an outer frame 320 and an innerframe 350. As discussed above for valves 100 and 200, the outer frame320 and the inner frame 350 of valve 300 can each be formed with ashape-memory material and have a biased expanded configuration. Theouter frame 320 and the inner frame 350 can be moved to a collapsedconfiguration for delivery of the valve 300 to the heart. In thisexample method of preparing the valve 300 for delivery to the heart, theouter frame 320 of the valve 300 is first disposed in a prolapsed orinverted configuration as shown in FIG. 16. Specifically, the elastic orsuperelastic structure of outer frame 320 of valve 300 allows the outerframe 320 to be disposed in the prolapsed or inverted configurationprior to the valve 300 being inserted into the lumen of the deliverysheath 326. As shown in FIG. 16, to dispose the outer frame 320 in theinverted configuration, the outer frame 320 is folded or inverteddistally (to the right in FIG. 16) such that an open free end 316 of theouter frame 320 is pointed away from an open free end 347 of the innerframe 350. As described above for valve 100, in this invertedconfiguration, the overall outer perimeter or outer diameter of thevalve 300 is reduced and the overall length is increased. For example,the diameter D1 shown in FIG. 15 is greater than the diameter D2 shownin FIG. 16, and the length L1 (shown in FIG. 12 for valve 200) is lessthan the length L2 shown in FIG. 16 for valve 300. With the outer frame320 in the inverted configuration relative to the inner frame 350, thevalve 300 can be placed within a lumen of a delivery sheath 326 as shownin FIG. 17 for delivery of the valve 300 to the left atrium of theheart. By disposing the outer frame 320 in the inverted configurationrelative to the inner frame 350, the valve 300 can be collapsed into asmaller overall diameter, i.e. when placed in a smaller diameterdelivery sheath, than would be possible if the valve 300 in theconfiguration shown in FIG. 15 were collapsed radially without beinginverted. This is because in the configuration shown in FIG. 15, the twoframes are concentric or nested, and thus the outer frame 320 must becollapsed around the inner frame 350, whereas in the configuration shownin FIG. 16, the two frames are substantially coaxial but not concentricor nested. Thus, in the configuration shown in FIG. 16 the outer frame320 can be collapsed without the need to accommodate the inner frame 350inside of it. In other words, with the inner frame 350 disposed mostlyinside or nested within the outer frame 320, the layers or bulk of theframe structures cannot be compressed to as small a diameter. Inaddition, if the frames are nested, the structure is less flexible, andtherefore, more force is needed to bend the valve, e.g. to pass throughtortuous vasculature or to make tight turn in the left atrium afterpassing through the atrial septum to be properly oriented for insertioninto the mitral valve annulus.

FIGS. 22-24 illustrate a portion of a procedure to deliver the valve 300to the heart. In this embodiment, the valve 300 is shown being deliveredvia a transfemoral delivery approach as described, for example, in the'572 PCT application and/or in the '305 PCT Application incorporated byreference above. The delivery sheath 326, with the valve 300 disposedwithin a lumen of the delivery sheath 326 and in an invertedconfiguration as shown in FIG. 17, can be inserted into a femoralpuncture, through the femoral vein, through the inferior vena cava, intothe right atrium, through the septum Sp and into the left atrium LA ofthe heart. With the distal end portion of the delivery sheath 326disposed within the left atrium of the heart, the valve 300 can bedeployed outside a distal end of the delivery sheath 326. For example,in some embodiments, a pusher device 338 can be used to move or push thevalve 300 out the distal end of the delivery sheath 326. As shown inFIGS. 22-24, a tether 336 can be attached to the valve 300, and extendthough the mitral annulus, through the left ventricle LV, and out apuncture site at the apex Ap. In some embodiments, the valve 300 can bemoved out of the delivery sheath 326 by pulling proximally on the tether336. In some embodiments, the valve 300 can be deployed by pushing withthe pusher device and pulling with the tether.

As the valve 300 exits the lumen of the delivery sheath 326, the outerframe assembly 310 exits first in its inverted configuration as shown inthe progression of FIGS. 18-20 (see also FIG. 22). After the outer frameassembly 310 is fully outside of the lumen of the delivery sheath 326,the outer frame 320 can revert to its expanded or deployed configurationas shown in FIGS. 21, 23 and 24. In some embodiments, the outer frame320 can revert automatically after fully exiting the lumen of thedelivery sheath due to its shape-memory properties. In some embodiments,a component of the delivery sheath or another device can be used to aidin the reversion of the outer frame assembly 310. In some embodiments,the pusher device and/or the tether can be used to aid in the reversionof the outer frame assembly 310. The valve 300 can continue to bedeployed until the inner frame 350 is fully deployed with the leftatrium and the valve 300 is in the expanded or deployed configuration(as shown, e.g., in FIGS. 15 and 24). The valve 300 and the tether 336can then be secured to the apex of the heart with an epicardial paddevice 339 as shown in FIG. 24 and as described in more detail in the'572 PCT application and the '305 PCT application.

FIG. 25 illustrates schematically another embodiment of a deliverysystem that can be used to delivery and deploy a prosthetic heart valvewithin a heart of a patient with, for example, a transvascular approach.In this embodiment, a delivery system 405 includes a delivery sheath426, a valve holder 438 (also referred to as a “pusher”), and one ormore actuation wires 474 and 476. In this schematic illustration, onlytwo actuation wires are illustrated, but in other embodiments, only oneactuation wire or more than two actuation wires can be used.

The delivery sheath 426 can be used to deliver a valve 400 that includesan inner valve assembly 440 including an inner frame (not labeled inFIG. 25) and an outer frame assembly 410 including an outer frame (notlabeled in FIG. 25). The valve 400 can be constructed the same as orsimilar to, and function the same as or similar to, for example, any ofthe prosthetic valves described herein and/or in the '305 PCTApplication, and can be moved between a deployed or expandedconfiguration and a delivery configuration in which the outer frame isdisposed in an inverted positon relative to the inner frame as describedherein and/or in the '305 PCT Application. As shown in FIG. 25, thevalve 400 can be disposed within a lumen of the delivery sheath 426 whenthe valve is in the delivery configuration (i.e., the outer frame isinverted relative to the inner frame). In this embodiment, when in thedelivery configuration and placed within a delivery sheath, the outerframe assembly 410 is disposed distal of the inner valve assembly 440.The valve holder 438 is coupled to the inner valve assembly 440 and theactuation wires are coupled to the outer fame assembly 410. The valveholder 438 can be releasably coupled to the inner valve assembly 440 viacouplers 406 that are attached to the inner valve assembly 440 as shownin FIGS. 26A-26C. In this embodiment, the couplers 406 are in the formof a T-bar or hammer shape. It should be understood that couplers withother configurations and shapes can be used.

As shown in FIG. 26A, the couplers 406 are received within the recesses404 and the valve 400 and the valve holder 438 can be disposed withinthe lumen of the delivery sheath 426. The inner diameter of the deliverysheath 426 can be sized such that when the valve holder 438 and valve400 are disposed therein, the couplers 406 are unable to exit therecesses 404. In other words, the inner walls of the delivery sheath 426maintain the couplers 406 within the recesses 404. When the valve 400 ismoved outside of the delivery sheath 426, the couplers 406 will be ableto freely exit the recesses 404 releasing the inner frame 450 from thevalve holder 438.

In alternative embodiments, the valve holder 438 can be removablycoupled to the valve 400 (e.g., the inner frame 450 of the valve 400)via wires or sutures that can be cut after delivery of the valve 400 tothe heart. In some cases, the valve holder 438 can be decoupled from thevalve 400 when the valve is still disposed within the delivery sheath426, while in other instances the valve holder 438 can be decoupled fromthe valve 400 after the valve 400 exits the delivery sheath 426 withinthe heart.

The actuation wires 474 and 476 can be coupled to the outer frame of theouter frame assembly 410 with a variety of different coupling methods.For example, the outer frame 410 can include loops (as described hereinwith respect to outer frame 510, outer frame 1010, and in the '305 PCTApplication) through which the actuation wires 474 and 476 can bereceived or threaded. The number of loops on the outer frame can varyand the number of loops through which each actuation wire is connectedcan vary. For example, in some embodiments, the outer frame includes 12loops and a first actuation wire is threaded through 6 of the loops anda second actuation wire is threaded through 6 of the loops. In otherembodiments, the outer frame can include 12 loops and there can be 4actuation wires, each coupled to 3 of the loops. In some embodiments, asingle actuation wire is coupled through all of the loops of the outerframe.

In this embodiment, the delivery sheath 426 can be used to deliver thevalve 400 to the left atrium of the heart using a transvascular approach(e.g., transfemoral, transatrial, transjugular). When the distal end ofthe delivery sheath 426 is disposed within the left atrium, the valve400 is moved out of the lumen of the delivery sheath 426 using theactuation wires 474, 476 to assist in pulling the valve 400 out of thedelivery sheath 426. In some cases, the valve holder 438 can also beused to push the valve 400 out of the delivery sheath 426. Morespecifically, the actuation wires 474 and 476 can extend from the outerframe assembly 410 out a distal end of the delivery sheath and extendproximally. In some embodiments, the actuation wires 474, 476 extendproximally outside the delivery sheath 426, then pass back into thelumen of the delivery sheath 426 through side apertures or holes (notshown) and then out a proximal end of the delivery sheath 426. Thus, auser (e.g., physician) can pull the proximal end portions of theactuation wires 474 and 476 to in turn pull the outer frame assembly 410out of the distal end of the delivery sheath 426. In some embodiments,the actuation wires 474, 476 extend proximally from the outer frameassembly 410, back through the distal end of the delivery sheath 426(e.g., rather than through side apertures or holes of the deliverysheath) and within the lumen of the delivery sheath, and then out aproximal end of the delivery sheath 426. Various different embodimentsand configurations are described in more detail below.

As the outer frame assembly 410 exits the delivery sheath 426 it willstill be in an inverted configuration relative to the inner valveassembly 440. After the outer frame assembly 410 is at least partiallyoutside of the lumen of the delivery sheath 426, the outer frameassembly 410 can begin to revert to its expanded or deployedconfiguration (not shown in FIG. 25). In this embodiment, however, theactuation wires 474 and 476 can function to selectively (e.g., by anoperator) assist and/or control the expansion, deployment and/orarticulation of the valve 400 as the valve 400 is delivered to theheart. In this manner, in use, the proximal end portions of theactuation wires 474, 476 can be pulled distally to manipulate the outerframe assembly 410 to assist and control the transition of the outerframe assembly 410 from its inverted configuration relative to the innervalve assembly 440 to its expanded or deployed configuration (notshown). In some embodiments, the actuation wires 474, 476 can bemanually grasped by a user to pull the actuation wires proximally. Insome embodiments, the actuation wires 474, 476 can be operativelycoupled to the delivery system 405 such that the user does not have tomanually handle the actuation wires. For example, the actuation wirescan be coupled to a delivery sheath and/or to a handle assembly (notshown) of the delivery system 405. Various embodiments of a deliverysystem are described in more detail below and in the '305 PCTApplication.

FIG. 27 illustrates an embodiment of a delivery system 505 that can beused to deliver and deploy a prosthetic heart valve 500 (also referredto herein as “valve”) within a heart in a procedure similar to or thesame as the procedures described with respect to other embodimentsdescribed herein (e.g., the embodiments illustrated in and describedwith respect to FIGS. 34-42) and embodiments described in the '305 PCTApplication. Thus, some details regarding the valve 500 and proceduresperformed therewith are not described herein. It should be understoodthat for features and functions not specifically discussed, thosefeatures and functions can be the same as or similar to the valvesdescribed herein (e.g., the valve 1000) and/or in the '305 PCTApplication. The valve 500 can be constructed the same as or similar to,and function the same as or similar to any of the valves describedherein and/or in the '305 PCT Application. For example, the valve 500includes an outer frame assembly that has an outer frame 520, an innervalve assembly 540 that has an inner frame 550, and a tether 536 coupledto the inner valve assembly. The delivery system 505 includes an outerdelivery sheath 526, an inner sheath 508, a valve holder 538 (alsoreferred to as a “pusher”) and a multi-lumen elongate tube member 503(also referred to as “tube” or “tube member” or “multi-lumen elongatemember”). As shown in FIG. 27, the inner sheath 508 is movably disposedwithin the lumen 582 defined by the outer delivery sheath 526, and thetube member 503 is movably disposed within a lumen 583 defined by theinner sheath 508. The valve holder 538 is movably disposed the lumen 583defined by the inner sheath 508.

As with other embodiments described herein and embodiments of the '305PCT Application, the valve 500 can be moved from a biased expandedconfiguration to an inverted configuration for delivery of the valve 500to the heart. More specifically, to place the valve 500 in the invertedconfiguration, the outer frame 520 can be moved to an invertedconfiguration relative to the inner frame 550. In this embodiment, thevalve 500 is placed at least partially within the lumen of the innersheath 508 when the valve 500 is in the inverted configuration, anddisposed near a distal end of the inner sheath 508. The valve holder 538is also disposed within the lumen 583 of the inner sheath 508. The innerframe 550 can be releasably coupled to the valve holder 538 withcouplers 506 in the same or similar manner as described above withrespect to couplers 406, couplers 1006, and/or any of the couplersdescribed in the '305 PCT Application. Similarly, the outer frame 520includes loops 562 through which actuation wires 574-577 can be threadedthrough in the same or similar manner as described herein (e.g., withrespect to valve 1000) and/or in the '305 PCT Application. The innersheath 508 is movably disposed within the outer delivery sheath 526. Asshown in FIG. 6, a portion of the valve 500 is disposed outside of theinner sheath 508 and within the lumen 582 of the outer delivery sheath526. In some cases, the entire valve 500 can be disposed within thelumen 583 of the inner sheath 508 prior to performing the procedure todeploy the valve.

In this embodiment, the inner sheath 508 defines side apertures 509through which the actuation wires 574-577 can pass through. Morespecifically, as shown in FIG. 27, when the valve 500 is disposed withinthe lumen 583 of the inner sheath 508, the actuation wires 574-577extend proximally from the outer frame 520, along the outside of theinner sheath 508 and within the lumen 582 of the outer delivery sheath526, back through side apertures 509 defined by the inner sheath 508,within the lumen 583 of the inner sheath 508, and are pinned by anelongate pinning member 578-1, 578-2, 578-3, 578-4 (collectivelyreferred to as pinning member 578; pinning members 578-3 and 578-4 arenot shown in FIG. 27; for illustrative purposes, refer to pinningmembers 1078-3 and 1078-4 shown in and described with respect to FIGS.35-37A) to the tube member 503. As shown, a first end of the actuationwire 574 and a first end of the actuation wire 575 are pinned by apinning member 578-2, and a first end of the actuation wire 576 and afirst end of the actuation wire 577 are pinned by a pinning member578-1. A second end of the actuation wire 574 and a second end of theactuation wire 576 are pinned by a pinning member 578-4 (not shown), anda second end of the actuation wire 575 and a second end of the actuationwire 577 are pinned by a pinning member 578-3 (not shown).

The actuation wires 574-577 can be pinned to the tube member 503 by thepinning members 578-1, 578-2, 578-3, 578-4 in the same or similar manneras described below with respect to the delivery system 1005. Thus, somedetails regarding, for example, the tube member 503, the pinning member578-1, 578-2, 578-3, 578-4 and the actuation wires 574-577, andprocedures performed therewith, are not described with respect to thisembodiment. It should be understood that for features and functions notspecifically discussed with respect to this embodiment, those featuresand functions can be the same as or similar to the delivery systemsdescribed in herein (e.g., the delivery system 1005) and/or in the '305PCT Application.

A user (e.g., physician) can use the tube member 503, to which theactuation wires 574-577 are coupled, to control and/or manipulatemovement and/or deployment of the valve 500 as described, for example,with respect to the delivery system 1005. In this embodiment, as shown,at least a portion of the actuation wires 574-577 can be disposed withinthe interior of the delivery sheath 526, thus limiting the exposure ofthe actuation wires 574-577 to areas external to the delivery sheath 526for at least a portion of the delivery and/or deployment of the valve500. Although the side apertures 509 defined by the inner sheath 508 areshown as disposed at or near the distal end portion of the inner sheath508, in other embodiments, side apertures 509 can be disposed at anysuitable location along the length of the inner sheath 508 (e.g.,towards a middle portion or a proximal portion of the managementsheath).

In this embodiment, to deliver the valve 500 to the heart, the distalend of the outer delivery sheath 526, with the valve 500, inner sheath508, valve holder 538, and tube member 503 disposed therein, is disposedwithin the left atrium of the heart. With the distal end portion of thedelivery sheath 526 disposed within the left atrium of the heart, thevalve 500 can be deployed outside of the delivery sheath 526. Forexample, the inner sheath 508, valve holder 538, and tube member 503 canbe moved distally relative to the outer sheath 526, moving or pushingthe valve 500 outside the lumen 582 of the outer sheath 526. Inaddition, or alternatively, the outer sheath 526 can be moved or pulledproximally, leaving at least a portion of the valve 500 disposed withinthe heart. In some instances, the tether 536 coupled to the valve 500can be used to help pull the valve 500 out of the lumen 582 of the outersheath 526.

As described in other embodiments herein and embodiments of the '305 PCTApplication, as the outer frame 520 becomes unconstrained by the outersheath 526, the outer frame 520 can begin to revert to its expanded oruninverted configuration. The actuation wires 575-577 can be used tocontrol the reversion of the outer frame 520. More specifically, afterthe outer frame 520 is disposed at least partially outside the distalend of the outer sheath 526, the tube member 503 can be pulledproximally such that the actuation wires (pinned to the tube member 503)pull the distally disposed portion of the outer frame 520 proximally(the same as or similar to as shown in FIG. 40) in a controlled mannerand such that the reversion of the outer frame 520 from its invertedconfiguration relative to the inner frame 550 can be controlled.

In addition, in some instances, the actuation wires 574-577 can assistin the articulation and placement of the valve 500 into its destination(e.g., a native annulus of an atrioventricular valve of a heart). Forexample, the actuation wires 574-577 can also be used to constrain,collapse, or otherwise move the valve 500 (e.g., radially compress theouter frame 520 of the valve 500) after the valve 500 exits the outersheath 526 and is in its reverted, expanded or partially expandedconfiguration. More specifically, in this embodiment, the tube member503 with the actuation wires 574-577 pinned thereto, can be manipulatedby a user to move or urge the outer frame 520 to a more compressedconfiguration (similar to or the same as shown in FIG. 41) by pulling ormoving the tube member 503 proximally. This may be desirable, forexample, to reposition the valve 500 within the heart before fullydeploying the valve 500.

With the outer frame 520 of the valve 500 disposed in its non-invertedand at least partially expanded configuration, and in a desired positonwithin the heart, the inner frame 550 can be deployed. As described inthe '305 PCT Application with respect to valve 2100, to decouple theinner frame 550 from the valve holder 538, the valve holder 538 can bemoved distally and/or the inner sheath 508 can be moved proximally suchthat the valve holder 538 is disposed outside of the lumen 583 of theinner sheath 508. As such, the couplers 506 can be released from therecesses 504, releasing or decoupling the inner frame 550 from the valveholder 538. In some embodiments, the tether 536 can be pulled to helpmove the inner frame 550 outside of the inner sheath 508. When the innerframe 550 is released from the valve holder 538 and disposed outside theinner sheath 508, the inner frame 550 can assume its biased expandedconfiguration.

The actuation wires 574-577 can also be released or decoupled from theouter frame 520 before or after the inner frame 550 is released form thevalve holder 538. To decouple the actuation wires 574-577 from the outerframe 520, one end of each of the actuation wires 574-577 can beunpinned or decoupled from the tube member 503. For example, the pinningmember 578-3 can be withdrawn proximally from a groove of the tubemember 503 (the same as or similar to the groove 1084 shown in anddescribed with respect to the delivery system 1005) such that the secondend of the actuation wire 577 and the second end of the actuation wire575 are each released or unpinned from the tube member 503, but remainpinned by pinning members 578-2 and 578-1, respectively. Similarly, thepinning member 578-4 can be withdrawn proximally from the groove suchthat the second end of the actuation wire 574 and the second end ofactuation wire 576 can each be released or unpinned from the tube member503, but remain pinned by pinning members 578-2 and 578-1, respectively.With one end of each of the actuation wires 575-577 coupled to the tubemember 503 (via pinning members 578-1 and 578-2 in this example), thetube member 503 can be pulled proximally, which in turn will pull theopposite ends of the actuation wires 574-577 out of the loops 562 ofouter frame 520. Thus with the actuation wires 574-577 detached from theouter frame 520, the outer frame can assume a biased expanded orpartially expanded configuration.

Although in the above example, the pinning members 578-3 and 578-4 aredescribed as being withdrawn to release the ends of the actuation wires574-577, alternatively, the pinning members 578-1 and 578-2 can bewithdrawn leaving the actuation wires 574-577 pinned by pinning members578-3 and 578-4. Further, the actuation wires 574-577 can be decoupledfrom the outer frame 520 at any suitable sequence or time period withinthe procedure. For example, in some instances it may be desirable forthe actuation wires 574-577 to be released after the valve 500 has atleast partially exited the delivery sheath 526 but before the valve 500is seated within the native annulus of the atrioventricular valve. Inother instances, for example, the actuation wires 574-577 can bereleased after the valve 500 has at least partially exited the outerdelivery sheath 526 and after the valve 500 is seated within the nativeannulus of the atrioventricular valve.

In some instances, for example as shown in FIG. 28, a delivery system505′ can include a dilator device or member 511′. The dilator 511′ canbe, for example, a balloon dilator and can be configured to expand anopening or passage, for example, during delivery of the prosthetic valve500′. The dilator device 511′ can be the same as or similar to thedilator device 1711 and used in the same or similar manner as describedin the '305 application with respect to FIGS. 43-48 and the method ofdelivery of FIG. 72. Delivery system 505′ can include the same as orsimilar features, and function the same as or similar to, for example,the delivery system 505 and/or the delivery system 1005 described hereinand/or delivery systems described in the '305 PCT Application.

In some embodiments, a prosthetic heart valve (e.g., any prostheticheart valve described herein and/or in the '305 PCT Application) caninclude an outer frame having multiple rows of loops through which anysuitable number of actuator wires can be routed and/or slidably disposed(e.g., to control the reversion profile and timing of the outer frame asit is deployed and delivered from a delivery sheath). FIGS. 29A and 29Billustrate such an embodiment of a prosthetic heart valve 600 and adelivery system 605 that can be used to deliver and deploy theprosthetic heart valve 600 (also referred to herein as “valve”) within aheart in a procedure similar to or the same as the procedures describedherein with respect to other embodiments and embodiments described inthe '305 PCT Application. Thus, some details regarding the valve 600 andprocedures performed therewith are not described herein. It should beunderstood that for features and functions not specifically discussed,those features and functions can be the same as or similar to the valvesand/or delivery system components described herein and/or in the '305PCT Application. For example, the valve 600 can be constructed the sameas or similar to, and function the same as or similar to any of thevalves described herein and/or in the '305 PCT Application. For example,the valve 600 includes an outer frame assembly that has an outer frame620, and an inner valve assembly that has an inner frame 650. As shownin FIGS. 29A and 29B, the delivery system 605 includes an outer deliverysheath 626. The delivery system 605 can also include other componentsand features not shown in FIGS. 29A and 29B, such as, for example, aninner sheath similar to inner sheath 508, a valve holder similar tovalve holder 538 described herein, and/or any other suitable componentsand/or features described with respect to other embodiments herein andin the '305 PCT Application.

As with other embodiments described herein and embodiments of the '305PCT Application, the valve 600 can be moved from a biased expandedconfiguration to an inverted configuration for delivery of the valve 600to the heart, as shown in FIG. 29A. In this embodiment, the valve 600 ispositioned for transvascular delivery similar to as described for valve500 above. Thus, when disposed in the inverted configuration within thesheath 626, the outer frame is disposed distal of the inner frame. Inthis embodiment, the outer frame 620 includes a first row of loops 662and a second row of loops 664, through which actuation wires 674-679 canbe threaded through in the same or similar manner as described hereinwith respect to valve 400 and/or valve 1000 and/or in the '305 PCTApplication with respect to valve 2100.

In this embodiment, the actuation wires 674-679 extend proximally fromthe outer frame 620, within the lumen 682 of the outer delivery sheath626, and out the proximal end of the outer delivery sheath 626. Inalternative embodiments, the actuator wires 674-679 can be pinned to atube member by pinning members (not shown in FIGS. 29A and 29B) in thesame or similar manner as described herein with respect to the deliverysystem 505 and/or the delivery system 1005.

In this embodiment, to deliver the valve 600 to the heart, the distalend of the outer delivery sheath 626, with the valve 600 disposedtherein, is disposed within the left atrium of the heart. With thedistal end portion of the outer delivery sheath 626 disposed within theleft atrium of the heart, the valve 600 can be deployed outside of theouter sheath 626. For example, the valve 600 can be moved distallyrelative to the outer sheath 626 outside the lumen 682 of the outersheath 626. In addition, or alternatively, the outer sheath 626 can bemoved or pulled proximally, leaving at least a portion of the valve 600disposed within the heart. In some embodiments, a tether (not shown)coupled to the valve 600 can be used to help pull the valve 600 out ofthe lumen 682 of the outer sheath 626.

As described in previous embodiments and embodiments of the '305 PCTApplication, as the outer frame 620 becomes unconstrained by the outersheath 626, the outer frame 620 can begin to revert to its expanded oruninverted configuration. The actuation wires 674-679 can be used tocontrol the reversion of the outer frame 620. More specifically, afterthe outer frame 620 is disposed at least partially outside the distalend of the outer sheath 626, the proximal ends of the actuator wires674-679 can be pulled proximally, which will in turn pull the open endof the outer frame 620 (to which the actuation wires 674-679 arecoupled) distally to help revert the outer frame 620. For example, asdescribed with respect to other embodiments herein and in the '305 PCTApplication, a user (e.g., a physician) can pull the end portions of theactuator wires 674-679 to in turn move the outer frame 620 to itsreverted configuration, as shown in FIG. 29B. Similarly stated, theactuation wires (coupled to the outer frame 620) pull the distallydisposed portion of the outer frame 620 proximally (the same as orsimilar to as shown in FIG. 40) in a controlled manner and such that thereversion of the outer frame 620 from its inverted configurationrelative to the inner frame 650 can be controlled. Having multiple rowsof loops (e.g., the first row of loops 662 and the second row of loops664), as shown and described with respect to this embodiment, providesincreased control of the reversion of the outer frame 620 from itsinverted configuration.

In this embodiment, the outer frame 620 has two rows of loops, each rowhaving 12 loops. In alternative embodiments, however, an outer frame canhave any suitable number of loops and/or rows of loops such that theouter frame 620 can be reverted in a controlled manner. For example, insome alternative embodiments, an outer frame can have 3 or more rows ofloops. Further, in some embodiments, the loops can be integrally ormonolithically formed with the outer frame, while in other embodiments,one or more of the loops can be formed separately from and coupled tothe outer frame (e.g., sewn onto the outer frame).

In addition, in some instances, the actuation wires 674-679 can assistin the articulation and placement of the valve 600 into its destination(e.g., a native annulus of an atrioventricular valve of a heart). Forexample, the actuation wires 674-679 can also be used to constrain,collapse, or otherwise move the valve 600 (e.g., radially compress theouter frame 620 of the valve 600) after the valve 600 exits the outersheath 626 and is in its reverted, expanded or partially expandedconfiguration.

With the outer frame 620 of the valve 600 disposed in its non-invertedand at least partially expanded configuration (see e.g., FIG. 29B), andin a desired positon within the heart, the inner frame 650 can bedeployed and allowed to assume its biased expanded configuration. Theactuation wires 674-679 can also be released or decoupled from the outerframe 620 before or after the inner frame 650 is deployed. To decouplethe actuation wires 674-679 from the outer frame 620, one end of each ofthe actuation wires 674-679 can be pulled proximally, which in turn willpull the opposite ends of the actuation wires 674-679 out of the loops674-679 of the outer frame 620. With the actuation wires 674-679detached from the outer frame 620, the outer frame can assume a biasedexpanded or partially expanded configuration.

In some instances, the actuation wires 674-679 can be decoupled from theouter frame 620 at any suitable sequence or time period within theprocedure. For example, in some instances it may be desirable for theactuation wires 674-677 to be released after the valve 600 has at leastpartially exited the delivery sheath 626 but before the valve 600 isseated within the native annulus of the atrioventricular valve. In otherinstances, for example, the actuation wires 674-679 can be releasedafter the valve 600 has at least partially exited the outer deliverysheath 626 and after the valve 600 is seated within the native annulusof the atrioventricular valve.

The embodiments described above and in the '305 PCT Application aredescribed for use in transfemoral delivery. In other embodiments,similar delivery devices and methods can be used for transapicaldelivery of a prosthetic heart valve. The following apparatus andmethods are described herein for use in transapical delivery anddeployment of prosthetic heart valves, such as prosthetic mitral valves,that can be configured to be moved to an inverted configuration fordelivery of the prosthetic valve to within a heart of a patient. Asdescribed herein, in some embodiments, a prosthetic valve includes anouter frame that can be inverted relative to an inner frame when theprosthetic valve is in a biased expanded configuration. The prostheticmitral valve can be formed with, for example, a shape-memory material.After inverting the outer frame, the prosthetic valve can be insertedinto a lumen of a delivery sheath such that the prosthetic valve ismoved to a collapsed configuration.

The delivery sheath can be used to deliver the prosthetic valve towithin a patient's heart using a variety of different deliveryapproaches for delivering a prosthetic heart valve (e.g., a prostheticmitral valve) where the inverted prosthetic valve would enter the heartthrough the ventricle of the heart and into the atrium of the heart. Forexample, as described in further detail herein with respect to FIGS.30A-30D and FIGS. 31A and 31B, an inverted prosthetic valve can bedelivered using an apical approach, i.e., delivered through the apex ofthe left ventricle of a heart.

After the delivery sheath has been disposed within the left atrium ofthe heart (e.g., via an apical approach), the prosthetic mitral valve ismoved distally out of the delivery sheath such that the inverted outerframe reverts and the prosthetic valve assumes its biased expandedconfiguration. The prosthetic mitral valve can then be positioned withina mitral annulus of the heart.

FIGS. 30A and 30B are schematic illustrations of a portion of aprosthetic heart valve 700, according to an embodiment, shown in a firstconfiguration and a second configuration respectively, and FIGS. 30C and30D illustrate the portions of the prosthetic heart valve 700 of FIGS.30A and 30B, respectively, shown disposed within a lumen of a deliverysheath 726′ and 726, respectively. FIGS. 31A and 31B illustrate aportion of the prosthetic heart valve 700 in the first configuration andsecond configuration of FIGS. 30A and 30B, respectively, and show lengthdimensions for the prosthetic heart valve in each of the firstconfiguration and the second configuration. The prosthetic heart valve700 (also referred to herein as “prosthetic valve” or “valve”) can be,for example, a prosthetic mitral valve. The valve 700 includes an outerframe 720 and an inner frame 750. The outer frame 720 and the innerframe 750 are each formed as a tubular structure similar to as describedin more detail above with respect to previous embodiments and/or withreference to the prosthetic valves in the '305 PCT Application. Theouter frame 720 and the inner frame 750 can be coupled together atmultiple coupling joints 746 disposed about a perimeter of the innerframe 750 and a perimeter of the outer frame 720. The valve 700 can alsoinclude other features, such as any of those described herein and/or inthe '305 PCT Application. For illustration purposes, only the innerframe 750 and the outer frame 720 are discussed with respect to FIGS.30A-31B. The various characteristics and features of valve 700 describedwith respect to FIGS. 30A-31B can apply to any of the prosthetic valvesdescribed herein.

The outer frame 720 is configured to have a biased expanded orundeformed shape and can be manipulated and/or deformed (e.g.,compressed or constrained) and, when released, return to its original(expanded or undeformed) shape. For example, the outer frame 720 can beformed of materials, such as metals or plastics, that have shape memoryproperties. With regards to metals, Nitinol® has been found to beespecially useful since it can be processed to be austenitic,martensitic or super elastic. Other shape memory alloys, such asCu—Zn—Al—Ni alloys, and Cu—Al—Ni alloys, may also be used. The innerframe 750 can be formed from a laser-cut tube of Nitinol®. The innerframe 750 can also have a biased expanded or undeformed shape and can bemanipulated and/or deformed (e.g., compressed and/or constrained) and,when released, return to its original (expanded or undeformed) shape.

The valve 700 can be delivered and deployed within a left atrium of aheart using a variety of different delivery approaches including, forexample, a transapical delivery approach, as described in more detailbelow, or, for example, a transatrial, transjugular or transfemoralapproach. As described above, in some situations, such as whendelivering a prosthetic valve to the heart via a transapical approach,it may be desirable to use a delivery sheath with a relatively smalllumen, and therefore, the size of the prosthetic valve during deliveryshould be sized accordingly. Thus, it is desirable to have a prostheticvalve that can be reconfigured between a biased expanded configurationfor implantation in the heart (e.g., within a native mitral annulus) anda delivery configuration that has a smaller outer perimeter or profileto allow for delivery within the lumen of the delivery sheath. Theprosthetic valve 700 and the embodiments of a prosthetic valve describedherein can be constructed and formed to achieve these desired functionsand characteristics.

More specifically, the valve 700 can have a biased expandedconfiguration (as shown in FIGS. 30A and 31A), an inverted configuration(as shown in FIGS. 30B and 31B), and a compressed or collapsedconfiguration (as shown in FIGS. 30C and 30D). The expandedconfiguration allows the valve 700 to function when implanted within theheart. The valve 700 can be moved to the inverted configuration and thecompressed or collapsed configuration for delivery of the valve 700 tothe heart of a patient.

To enable the valve 700 to be moved to the inverted configuration, theouter frame 720 can be coupled to the inner frame 750 in such a mannerto allow the outer frame 720 to move relative to the inner frame 750.More specifically, the coupling joints 746 can couple the outer frame720 to the inner frame 750 in such a manner to allow the outer frame 720to be moved relative to the inner frame 750. For example, in someembodiments, the coupling joints 746 can be configured to allow theouter frame 720 to rotate about the coupling joint 746 relative to theinner frame 750. In some embodiments, coupling joints can provide apivotal coupling between the outer frame 720 and the inner frame 750. Insome embodiments, the coupling joints can provide a flexible attachmentbetween the outer frame 720 and the inner frame 750. The coupling joints746 can be a variety of different types and configurations as describedin the '305 application incorporated herein with reference to thevarious embodiments of a prosthetic valve. For example, the couplingjoints 746 can include a living hinge, a flexible member, sutures, asuture wrapped through an opening, a pin or tab inserted through anopening or any combinations thereof.

To move the valve 700 from the expanded configuration (FIG. 30A) to theinverted configuration (FIG. 30B), the outer frame 720 is moved to aprolapsed or inverted configuration relative to the inner frame 750, asshown in FIGS. 30B, 30D and 31B, by moving (e.g., rotating, pivoting,flexing) the outer frame 720 about the coupling joints 746. The elasticor superelastic structure of outer frame 720 of valve 700 also allowsthe outer frame 720 to be moved to, and disposed in, the prolapsed orinverted configuration relative to the inner frame 750. To move theouter frame 720 to the inverted configuration relative to the innerframe 750, the outer frame 720 is folded or inverted proximally (to theright in FIG. 30B) relative to the inner frame 750 via the couplingjoints 746. As shown in FIGS. 30A and 31A, the outer frame 720 is in afirst position relative to the inner frame 750 prior to being invertedin which an open or free end portion 716 (also referred to the atriumportion 716 of the outer frame 720) is disposed distally or to the leftof the coupling joints 746 and in the same direction as a free endportion 747 (also referred to as a second end portion of the innerframe) of the inner frame 750. When the outer frame 720 is moved to aninverted configuration (i.e., second positon relative to the inner frame750), the free end portion 716 is disposed proximally of the couplingjoints 746 (or to the right in FIGS. 30B and 31B) and in an oppositedirection as the free end portion 747 of the inner frame 750. Saidanother way, when the valve 700 is in a biased expanded configuration(e.g., FIG. 30A), the coupling joints 746 are disposed between a firstend portion 744 (also referred to as a tether coupling portion) of theinner frame 750 and the free end portion 716 of the outer frame 720.When the valve 700 is in the inverted configuration (e.g., FIG. 30B)(i.e., the outer frame 720 has been moved to an inverted configurationor position), the coupling joints 746 are disposed between the free endportion or second end portion 747 of the inner frame 750 and the freeend portion 716 of the outer frame 720.

When in the inverted configuration, an overall length of the valve 700is increased, but a length of the inner frame 750 and a length of theouter frame 720 remains the same (or substantially the same). Forexample, as shown in FIGS. 31A and 31B an overall length L1 of the valve700 in the biased expanded configuration (prior to being inverted asshown in FIG. 31A) is less than the overall length L2 of the valve 700when in the inverted configuration (FIG. 31B). A length Li of the innerframe 750 and a length Lo of the outer frame 720 is substantially thesame (or the same) when the valve 700 is in both the biased expandedconfiguration and the inverted configuration. In addition, in someinstances, depending on the specific configuration of the outer frame,an overall outer perimeter or outer diameter of the valve 700 can besmaller when the valve 700 is in the inverted configuration.

With the valve 700 in the inverted configuration, the valve 700 can beplaced within a lumen of the delivery sheath 726 for delivery of thevalve 700 to the left ventricle and left atrium of the heart, as shownin FIG. 30D. When placed within the lumen of the delivery sheath 726,the valve 700 is moved to the collapsed or compressed configuration inwhich the outer diameter or outer perimeter of the valve 700 is reduced.Because the valve 700 is in the inverted configuration, the valve 700 isable to be placed within a smaller delivery sheath 726 than wouldotherwise be possible. For example, for comparison purposes, FIG. 30Cillustrates the valve 700 placed within a lumen of a delivery sheath726′ where the valve 700 has not been moved to an inverted configurationprior to being disposed within the delivery sheath 726′. As shown inFIG. 30C, an outer diameter of the valve 700 is reduced, but not to assmall of a diameter as for the valve 700 when placed in a deliverysheath 726 when in the inverted configuration. Thus, in FIG. 30C, thevalve 700 has an overall outer perimeter or outer diameter D1 and inFIG. 30D, the valve 700 has an overall outer perimeter or outer diameterD2, which is less than D1.

Thus, by disposing the outer frame 720 in the inverted configuration,the valve 700 can be collapsed into a smaller overall diameter, i.e.placed in a smaller diameter delivery sheath 726, than would be possibleif the valve 700 were merely collapsed radially. This is because whenthe valve is in the biased expanded configuration, the inner frame 750is nested within an interior of the outer frame 720, and thus the outerframe 720 must be collapsed around the inner frame 750. In someembodiments, the inner frame 750 and the outer frame are disposedconcentrically. Whereas in the inverted configuration, the inner frame750 and the outer frame 720 are arranged axially with respect to eachother (i.e., the inner frame is not nested within the outer frame 750),such that the outer frame 720 can be collapsed without needing toaccommodate all of the structure of the inner frame 750 inside it. Inother words, with the inner frame 750 disposed mostly inside or nestedwithin the outer frame 720, the layers or bulk of the frame structurescannot be compressed to as small a diameter. In addition, if the framesare nested, the structure is less flexible, and therefore, more force isneeded to bend the valve, e.g. to pass through tortuous anatomy or tomake turns through a patient to be properly oriented for insertion intothe mitral valve annulus.

FIG. 32A is a schematic illustration in side view of a delivery systemthat can be used to deliver and deploy a prosthetic heart valve within aheart of patient with, for example, a transapical approach. In thisembodiment, a delivery system 805 includes a delivery sheath 826, adilator 870, an elongate member 880, and two actuation wires 874 and876. FIG. 32B is a schematic illustration in front view of the elongatemember 880. In this schematic illustration, only two actuation wires areillustrated, but in other embodiments, only one actuation wire or morethan two actuation wires can be used.

The delivery sheath 826 can be used to deliver a valve 800 that includesan inner valve assembly 840 including an inner frame (not labeled inFIG. 32A and FIG. 32B) and an outer frame assembly 810 including anouter frame (not labeled in FIG. 32A and FIG. 32B). The valve 800 can beconstructed the same as or similar to, and function the same as orsimilar to, for example, the prosthetic valves described herein and/orin the '305 PCT Application, and can be moved between a deployed orexpanded configuration and a delivery configuration in which the outerframe is disposed in an inverted positon relative to the inner frame asdescribed above. As shown in FIG. 32A, the valve 800 can be disposedwithin a lumen of the delivery sheath 826 when the valve is in thedelivery configuration (i.e., the outer frame is inverted relative tothe inner frame and positioned proximal of the inner frame when in thedelivery sheath). The actuation wires 874, 876 are releasably coupled tothe outer frame assembly 810. In this manner, after delivery to andseating within the native annulus of the patient's heart, the actuationwires 874, 876 can be released from the outer frame assembly 810 andremoved from the patient, leaving the prosthetic heart valve implantedwithin the patient's heart, as described in more detail herein.

The dilator 870 has a fluid delivery portion 872 and a collapsibledilation portion 873 (also referred to herein as “dilation portion”).The fluid delivery portion 872 is configured to receive a fluid anddeliver the fluid to the dilation portion 873 to inflate the dilationportion 873. The dilation portion 873 is configured to be inflated suchthat when inflated it can dilate (e.g., expand an opening or passage) toone or more portions of the heart as the delivery system 805 isintroduced into the heart of the patient. For example, in use during atransapical delivery approach, the dilation portion 873, when inflated,can extend outside a distal end of the delivery sheath 826 and provide alead-in for the delivery sheath 826 and help open or enlarge the entryopening at the epicardial surface and ease entry through the mitralannulus without entangling the valve's chordae tendinae. With thedelivery sheath 826 placed at a desired position within the heart, thedilator portion 873 can be deflated and removed leaving the deliverysheath 826 within the heart.

The dilation portion 873 can have any suitable shape or size to dilate aportion of the heart (e.g., an incision in an apical portion of theheart) and thereby assist delivery of the valve 800 to the atrium of theheart. For example, in some embodiments, a dilation portion can have aconical and/or tapered shape with a rounded or blunt distal tip. Inother embodiments, a dilation portion can have a round shape, an ovalshape, triangular, or other suitable shape. Although not shown, in someembodiments, a dilator can define a guide wire lumen therethrough.During delivery of a prosthetic valve, for example, a guidewire can beextended through an apical portion of the heart, through the leftventricle and into the left atrium of the heart. In such an embodiment,the dilator can be threaded over the guidewire to be inserted into theheart. The guidewire can be any suitable size. For example, in someembodiments, the guidewire can be from about a 0.03″ guidewire to a0.04″ guidewire (e.g., a 0.035″ guidewire). An example dilator device isdescribed in U.S. patent application No. 14,527,382, filed Oct. 29, 2014(“the '382 application”), the entire disclosure of which is incorporatedherein by reference. As described in more detail herein, with thedelivery sheath 826 placed at the desired position within the heart, thedilator portion 873 can be deflated (by removing the fluid therefrom)and removed along the guidewire leaving the delivery sheath 826 withinthe heart.

The elongate member 880 can be used to flip the outer frame assembly 810and deliver to and retract from the heart at least a portion of thedilator 870. The elongate member 880 defines a dilator lumen 882configured to slidably receive the dilator 870. More specifically, thedilator lumen 882 is configured to slidably receive the delivery portion872, and the dilation portion 873 when deflated, as described in moredetail herein. The elongate member 880 further defines four actuatorwire lumens 884 (as shown in FIG. 32B) spaced radially apart from thedilator lumen 882 and configured to slidably receive the actuator wires874, 876. The elongate member 880 is slidably disposed within thedelivery catheter 826 and through a center portion of both the innervalve assembly 840 and the outer frame assembly 810. Although not shown,in some embodiments, the elongate member 880 can vary in size, e.g., itsouter diameter or perimeter can increase and/or decrease at variousportions of the elongate member 880. For example, in some embodiments, aportion of the elongate member 880 proximal to the valve 800, when theelongate member 880 is disposed within the delivery sheath 826 andextends through the center portions of the valve 800, can have a firstdiameter; and a portion of the elongate member 880 extending through thecenter portions (e.g., between the leaflets of the inner valve assembly840) of the valve 800 can have a second diameter smaller than the firstdiameter. In this manner, the reduced diameter of the portion of theelongate member 880 configured to be disposed through a portion of thevalve 800 can prevent or reduce potential undesirable interference withthe valve 800 by the elongate member 880. Similarly, portions of thedilator 870, e.g., the fluid delivery portion 872, can vary in size(e.g., diameter) corresponding to the size variations of the elongatemember 880.

The actuation wires 874, 876 can be coupled to the outer frame of theouter frame assembly 810 with a variety of different coupling methods.For example, the outer frame of the outer frame assembly 810 can includeloops (not shown in FIGS. 32A and 32B) through which the actuation wires874, 876 can be received or threaded. Such an outer frame is describedin the '305 PCT Application incorporated herein (see, e.g., FIG. 57) andwith respect to FIG. 27 herein. The number of loops on the outer framecan vary and the number of loops through which each actuation wire isconnected can vary. For example, in some embodiments, the outer frameincludes 12 loops and a first actuation wire (e.g., actuation wire 874)is threaded through 6 of the loops and a second actuation wire (e.g.,actuation wire 876) is threaded through 6 of the loops. In otherembodiments, the outer frame can include 12 loops and there can be 4actuation wires, each coupled to 3 of the loops. In some embodiments, asingle actuation wire is coupled through all of the loops of the outerframe.

To deliver and deploy the prosthetic valve 800 within a heart, thedelivery sheath 826 can be inserted through the epicardial surface ofthe patient's heart (e.g., at or near an apex region of the heart) andextended through the left ventricle and to the left atrium of the heart.Prior to inserting the delivery sheath 826 into the heart, with thedilation portion 873 of the dilator 870 extending outside a distal endof the delivery sheath 826, a fluid can be injected to the fluiddelivery portion 872 thereby inflating the dilation portion 873 of thedilator 870. The distal end portion (e.g., tapered distal end) of thedilation portion 873 can provide a lead-in for the delivery sheath 826and help open or enlarge the entry opening at the epicardial surface andthrough the mitral annulus. When the delivery sheath 826 is placed atthe desired position within the heart, the fluid can be at leastpartially withdrawn or removed from the dilation portion 873 therebydeflating the dilation portion 873, and the deflated dilation portion873 can be removed through the delivery catheter 826, leaving thedelivery sheath 826, the inner valve assembly 840 and the outer frameassembly 810 within the heart.

With the distal end of the delivery sheath 826 disposed within the leftatrium, the valve 800 can be moved out of the lumen of the deliverysheath 826 by withdrawing the delivery sheath 826 proximally and/orusing a pusher device to push the valve 800 out the distal end of thedelivery sheath 826 and/or using the elongate member 880 and actuationwires 874, 876 to assist in pulling the valve 800 out of the distal endof the delivery sheath 826. More specifically, with the actuation wires874, 876 coupled to the outer frame assembly 810, the ends of theactuation wires 874, 876 can extend distally from the outer frameassembly 810 out the distal end of the delivery sheath 826 and then passinto the actuation wire lumens 884 of the elongate member 880 via sideapertures or holes 886 (labeled in FIG. 32A) defined by the elongatemember 880. In some embodiments, rather than side openings, theactuation wires lumens extend out openings in a distal end of theelongate member 880. In other words, the lumens 884 can extend to thedistal end of the elongate member 880. The ends of the actuation wires874, 876 can then extend proximally through the actuation wire lumens884 of the elongate member 880 and out the proximal end of the elongatemember 880 and the proximal end of the delivery sheath 826. Morespecifically, each wire 874, 876 has two ends. A first end is held atthe proximal end of the elongate member 880, and the second end extendsdistally through a first actuation wire lumen 884, through the loops(not shown) of the outer frame assembly 810, back through a secondactuation wire lumen 884 and extends proximally out the proximal end ofthe elongate member 880. Thus, for an embodiment with two actuationwires and four actuation wire lumens, four ends of the actuation wireswill extend proximal of a distal end of the delivery system 305 orcoupled to a portion of the delivery system (e.g., a catheter orhandle). Thus, a user (e.g., physician) can pull the end portions of theactuation wires 874, 876 to in turn pull the outer frame assembly 810out of the distal end of the delivery sheath 826 as described in moredetail below.

In some embodiments, the end portions of the actuation wires 874, 876extend proximally from the proximal end of the elongate member 880 andare operably coupled to a handle (not shown). The handle can bemanipulated by a user to selectively pull and/or release the actuationwires 874, 876. In some embodiments, the handle can include one or moretoggle switches or similar mechanisms to help control the transition ofthe valve 800. In this manner, a user can use the handle to selectivelypull the valve 800 distally and out from the delivery sheath 826, andselectively control the flipping or transition between configurations ofthe outer frame assembly 810. In some embodiments, the end portions ofactuation wires extend proximally through actuation wire lumens of adelivery sheath and out the proximal end of an elongate member, butremain within the delivery sheath. In such embodiments, a handle orfunctionally similar actuation wire manipulator is operably coupled tothe actuation wires, and can be actuated and/or manipulated toselectively pull or release the actuation wires for delivery and/ordeployment of the valve 800, as described above.

During delivery of the valve 800, as the inner valve assembly 840 exitsthe distal end of the delivery sheath 826, the outer frame assembly 810will be in an inverted configuration relative to the inner valveassembly 840 (similar to as shown and described with respect to FIG.30B). After the inner valve assembly 840 is outside of the lumen of thedelivery sheath 826, the outer frame assembly 810 can begin to exit thelumen of the delivery sheath 826 and to revert to its expanded ordeployed configuration (similar to as shown, for example, with respectto FIG. 30A). In this embodiment, the actuation wires 874, 876 canfunction to selectively (e.g., by an operator) assist and/or control theexpansion and reversion profile of the valve 800 as the valve 800 isdelivered to the heart. For example, a distal end of the elongate member880 can be moved distally out of the delivery sheath 826, and the endportions (extending proximally out of the delivery sheath 826) of theactuation wires 874, 876 can be pulled proximally (or a handle coupledthereto can be manipulated), which in turn pulls the open end of theouter frame distally relative to the inner frame to help move the outerframe to its reverted expanded configuration. Thus the actuation wiresand elongate member 880 can be used to help manipulate the outer frameassembly 810 to assist and control the transition of the outer frameassembly 810 from its inverted configuration relative to the inner valveassembly 840 to its expanded or deployed configuration. In this manner,the profile of the valve 800 as the outer frame assembly 810 transitionsfrom its inverted configuration to its reverted, expanded or deployedconfiguration can be selectively minimized and/or otherwise manipulatedas desired by a user. Such control of the profile of the valve 800throughout its transition between configurations and during delivery anddeployment of the valve 800 can promote a safer, more repeatable andefficient valve delivery and deployment procedure. In some embodiments,the actuation wires 874, 876 can be manually grasped by a user to pullthe actuation wires proximally. In some embodiments, the actuation wires874, 876 can be operatively coupled to the delivery system 805 such thatthe user does not have to manually handle the actuation wires. Forexample, the actuation wires can be coupled to a delivery sheath and/orto a handle assembly (not shown) of the delivery system 805.

With the outer frame assembly 810 reverted relative to the inner valveassembly 840 such that the valve 800 is disposed in its deployedconfiguration within the annulus of the heart, the delivery system 805can be removed from the heart. For example, the actuation wires 874, 876can be decoupled from the outer frame assembly 810 and removed from theheart via the elongate member 880, and the elongate member 880 and thedelivery sheath 826 can be withdrawn from the heart, leaving the valve800 implanted within the annulus of the heart. More specifically, todecouple the actuation wires 874, 876 from the outer frame assembly 810and remove the actuation wires 874, 876 from the patient, a singleproximal end of the actuation wires 874, 876 can be pulled proximallysuch that the other proximal end of the actuation wires 874, 876 getspulled distally through the actuator wire lumens 884, out the aperturesor holes 886 in the elongate member 880, through the loops of the outerframe 820, and back out through the actuator wire lumens 884. In thismanner, the actuation wires 874, 876 can be removed from the elongatemember 880, the delivery sheath 826, and the patient after the actuationwires 874, 876 are used to facilitate delivery and deployment of thevalve 800 within the heart.

FIG. 33A is an illustration in side view of a delivery system 905 thatcan be used to delivery and deploy a prosthetic heart valve 900 within aheart of a patient with, for example, a transapical approach. Thedelivery system 905 can be constructed the same as or similar to, andfunction the same as or similar to, for example, the delivery system805. Further, the valve 900 can be constructed the same as or similarto, and function the same as or similar to, for example, any of theprosthetic valves described herein or any of the prosthetic valvesdescribed in the '305 PCT Application, and can be moved between adeployed or expanded configuration and a delivery configuration in whichthe outer frame is disposed in an inverted position relative to theinner frame as described herein with respect to the valve 800. As shownin FIG. 33A, the valve 900 is disposed in its inverted configuration andradially constrained within the delivery sheath prior to being deployedand implanted within a heart as described in more detail below. Further,as shown in FIG. 33B, the valve 900 is disposed in its reverted,deployed configuration after being delivered to the heart and before theactuation wires and delivery sheath have been removed. It should beunderstood that for features and functions not specifically discussedwith respect to the delivery system 905, those features and functionscan be the same as or similar to the delivery system 805 or any of thedelivery systems described herein. Similarly, it should be understoodthat for features and functions not specifically discussed with respectto the prosthetic valve 900, those features and functions can be thesame as or similar to the valve 800 or any of the valves described inthe '305 PCT Application.

The delivery system 905 includes a delivery sheath 926, a dilator 970,an elongate member 980, and two actuation wires 974 and 976. FIG. 33C isa distal end view of the elongate member 980. The delivery sheath 926can be used to deliver a valve 900 that includes an inner valve assembly940 including an inner frame (not labeled in FIG. 33A) and an outerframe assembly 910 including an outer frame (not labeled in FIG. 33A).

The elongate member 980 can be used to assist in the flipping of theouter frame assembly 910 and deliver to and retract from the heart atleast a portion of the dilator. As shown in FIG. 33C, the elongatemember 980 defines a dilator lumen 982 configured to slidably receivethe dilator 970. More specifically, the dilator lumen 982 is configuredto slidably receive the dilator 970 therethrough when the dilatorportion 973 is deflated. The elongate member 980 further defines fouractuator wire lumens 984 (as shown in FIG. 33C) spaced radially apartfrom the dilator lumen 982 and configured to receive the actuation wires974, 976. The elongate member 980 is slidably disposed within thedelivery catheter 926 and through a center portion of both the innervalve assembly 940 and the outer frame assembly 910. In alternativeembodiments, an elongate member can define any suitable number ofactuator wire lumens. For example, as shown in FIG. 33D, an elongatemember 980′ can define six actuator wire lumens 984′ spaced radiallyapart from the dilator lumen 982′. Similar to the actuator wire lumens984 discussed above, the six actuator wire lumens 984′ can be configuredto receive actuator wires (e.g., actuator wires 974 and 976). In yetalternative embodiments, actuator wire lumens can be configured toreceive any suitable number of actuator wires. For example, in someembodiments in which a delivery system includes an elongate memberdefining six actuator wire lumens (e.g., actuator wire lumens 984′), thedelivery system can include three actuator wires. In such embodiments,in some instances, each actuator wire can be routed through two actuatorwire lumens. Said another way, a first actuator wire can be routedthrough a first set of two actuator wire lumens; a second actuator wirecan be routed through a second set of two actuator wire lumens; and athird actuator wire can be routed through a third set of two actuatorwire lumens. Further, an elongate member can have any suitable shape(e.g., circular, oval, triangular, or the like). For example, as shownin FIG. 33D, the elongate member 980′ is circular.

In this embodiment, as shown, the actuation wires 974, 976 can bereleasably coupled to the outer frame of the outer frame assembly 910.For example, as shown in FIGS. 33A and 33B, the actuation wires 974, 976can be passed through loops 962 disposed around an open end portion ofthe outer frame assembly 910. More specifically, as described above, afirst end of each actuation wire 974, 976 is held at the proximal end ofthe elongate member 980, and the second end extends distally through afirst actuation wire lumen 984, through the loops 962 of the outer frameassembly 910, back through a second actuation wire lumen 984 and extendsproximally out the proximal end of the elongate member 980 (see e.g.,FIG. 33B).

To deliver and deploy the prosthetic valve 900 within a heart, thedelivery sheath 926 can be inserted through the epicardial surface ofthe patient's heart (e.g., at or near an apex region of the heart) andextended through the left ventricle and to the left atrium of the heart.Prior to inserting the delivery sheath 926 into the heart, with thedilation portion of the dilator extending outside a distal end of thedelivery sheath 926, a fluid can be injected to the fluid deliveryportion 972 thereby inflating the dilation portion 973 of the dilator970. The distal end portion (e.g., tapered distal end) of the dilationportion 973 can provide a lead-in for the delivery sheath 926 and helpopen or enlarge the entry opening at the epicardial surface and throughthe mitral annulus. When the delivery sheath 926 is placed at thedesired position within the heart, the fluid can be at least partiallywithdrawn or removed from the dilation portion 973 thereby deflating thedilation portion 973, and the deflated dilation portion 973 can beremoved through the delivery catheter 926, leaving the delivery sheath926, the inner valve assembly 940 and the outer frame assembly 910within the heart.

With the distal end of the delivery sheath 926 disposed within the leftatrium, the valve 900 can be moved out of the lumen of the deliverysheath 926 by, for example, withdrawing the delivery sheath 926proximally and/or moving the elongate member 980 distally and using theactuation wires 974, 976 to assist in pulling the valve 900 out of thedistal end of the delivery sheath 926. As described above for theprevious embodiment, the inner valve assembly 940 will exit the deliverysheath 926 first and then the outer frame assembly 910. Unconstrained bythe delivery sheath 926, the inner valve assembly 940 and outer frameassembly 910 can assume their biased expanded configurations.

To flip or revert the outer frame assembly 910, the elongate member 980can be moved distally out of the delivery sheath 926 as shown in FIG.33B. With the elongate member 980 moved distally, the proximal ends ofthe actuation wires 974, 976 can be pulled proximally, which will inturn pull the open end of the outer frame assembly 910 (to which theactuation wires 974, 976 are coupled) distally to help revert the outerframe. For example, as described above, a user (e.g., physician) canpull the end portions of the actuation wires 974, 976 to in turn movethe outer frame assembly 910 to its reverted configuration. In someembodiments, the end portions of the actuation wires 974, 976 extendproximally from the proximal end of the elongate member 980 and areoperably coupled to a handle (not shown). The handle can be manipulatedby a user to selectively pull and/or release the actuation wires 974,976. In some embodiments, the handle can include one or more toggleswitches or similar mechanisms to help control the transition of thevalve 900. In this manner, a user can use the handle to selectively pullthe valve 900 distally and out from the delivery sheath 926, andselectively control the flipping or transition between configurations ofthe outer frame assembly 910. In some embodiments, the end portions ofactuation wires extend proximally through actuation wire lumens of adelivery sheath and out the proximal end of an elongate member, butremain within the delivery sheath. In such embodiments, a handle orfunctionally similar actuation wire manipulator is operably coupled tothe actuation wires, and can be actuated and/or manipulated toselectively pull or release the actuation wires for delivery and/ordeployment of the valve 900, as described above.

As described above, as the valve 900 exits the distal end of thedelivery sheath 926, the outer frame assembly 910 will be in an invertedconfiguration relative to the inner valve assembly 940 (similar to asshown and described with respect to FIG. 30B). After the inner valveassembly 940 is outside of the lumen of the delivery sheath 926, theouter frame assembly 910 can begin to exit the lumen of the deliverysheath 926 and to revert to its expanded or deployed configuration (asshown in FIG. 33B). In this embodiment, the actuation wires 974, 976 canfunction to selectively (e.g., by an operator) assist and/or control theexpansion and reversion profile of the valve 900 as the valve 900 isdelivered to the heart. For example, a distal end of the elongate member980 can be moved distally out of the delivery sheath 926, and the endportions (extending proximally out of the delivery sheath 926) of theactuation wires 974, 976 can be pulled proximally (or a handle coupledthereto can be manipulated), which in turn pulls the open end of theouter frame distally relative to the inner frame to help move the outerframe to its reverted expanded configuration. Thus the actuation wires974, 976 and the elongate member 980 can be used to help manipulate theouter frame assembly 910 to assist and control the transition of theouter frame assembly 910 from its inverted configuration relative to theinner valve assembly 940 to its expanded or deployed configuration. Inthis manner, the profile of the valve 900 as the outer frame assembly910 transitions from its inverted configuration to its reverted,expanded or deployed configuration can be selectively minimized and/orotherwise manipulated as desired by a user. Such control of the profileof the valve 900 throughout its transition between configurations andduring delivery and deployment of the valve 900 can promote a safer,more repeatable and efficient valve delivery and deployment procedure.In some embodiments, the actuation wires 974, 976 can be manuallygrasped by a user to pull the actuation wires proximally. In someembodiments, the actuation wires 974, 976 can be operatively coupled tothe delivery system 905 such that the user does not have to manuallyhandle the actuation wires. For example, the actuation wires can becoupled to a delivery sheath and/or to a handle assembly (not shown) ofthe delivery system 905.

With the outer frame assembly 910 reverted relative to the inner valveassembly 940 such that the valve 900 is disposed in its deployedconfiguration (as shown in FIG. 33B) within the annulus of the heart,the delivery system 905 can be removed from the heart. For example, theactuation wires 974, 976 can be decoupled from the outer frame assembly910 and removed from the heart via the elongate member 980, and theelongate member 980 and the delivery sheath 926 can be withdrawn fromthe heart, leaving the valve 900 implanted within the annulus of theheart. More specifically, to decouple the actuation wires 974, 976 fromthe outer frame assembly 910 and remove the actuation wires 974, 976from the patient, a single proximal end of the actuation wires 974, 976can be pulled proximally such that the other proximal end of theactuation wires 974, 976 gets pulled distally through the actuator wirelumens 984, out the side apertures or holes 986 in the elongate member980 (each side aperture or hole 986 being in communication with acorresponding actuator wire lumen 984), through the loops 962 of theouter frame 920, and back out through the actuator wire lumens 984. Inthis manner, the actuation wires 974, 976 can be removed from theelongate member 980, the delivery sheath 926, and the patient after theactuation wires 974, 976 are used to facilitate delivery and deploymentof the valve 900 within the heart.

In some embodiments, after the valve 900 has been delivered and deployedwithin the heart, the delivery sheath 926 can be moved distally (beforeand/or after the actuation wires 974, 976 have been removed from theelongate member 980, the delivery sheath 926, and/or the patient) tocapture or otherwise engage with at least a proximal portion of thevalve 900 and at least partially collapse the proximal portion of thevalve. The delivery sheath 926 can then be used to move and/or reorient(e.g., rotate, clock, angle) the valve 900 within the heart. Forexample, a user can rotate the delivery sheath 926 about itslongitudinal axis to in turn rotate the valve 900 about its longitudinalaxis. In this manner, a user can ensure proper implantation of the valve900 within the heart without having to remove the valve 900 from theheart, for example, when the valve 900 is not first implanted in aproper manner.

FIGS. 34-42 illustrate a delivery system 1005 for delivering anddeploying a prosthetic heart valve, such as, prosthetic heart valve1000, within a heart, according to another embodiment. The prostheticheart valve 1000 (also referred to herein as “valve”) can be constructedthe same as or similar to, and function the same as or similar to any ofthe valves described herein. Thus, some details regarding the valve 1000are not described herein. As shown in FIG. 34, the valve 1000 has anouter frame assembly 1010 with an outer frame 1020 and an inner valveassembly 1040 with an inner frame 1050, and a tether 1036 coupled to theinner frame 1050. As described above for previous embodiments (e.g.,valve 100, 200, 300 etc.), the outer frame 1020 and the inner frame 1050of valve the 1000 can each be formed with a shape-memory material andhave a biased, expanded or deployed configuration. The outer frame 1020and the inner frame 1050 can be moved to a collapsed or undeployedconfiguration for delivery of the valve 1000 to the heart in which theouter frame 1020 is inverted relative to the inner frame 1050. Toprepare the valve 1000 for delivery to the heart, the outer frame 1020of the valve 1000 is first disposed in a prolapsed or invertedconfiguration as shown in FIG. 34. Specifically, the elastic orsuperelastic structure of outer frame 1020 of valve 1000 allows theouter frame 1020 to be disposed in the prolapsed or invertedconfiguration relative to the inner frame 1050 as described above, forexample with respect to valve 100.

For example, to dispose the outer frame 1020 in its invertedconfiguration relative to the inner frame 1050, the outer frame 1020 isfolded or inverted distally such that the outer frame 1020 is pointedaway from the inner frame 1050. With the outer frame 1020 in theinverted configuration, the valve 1000 can be placed within a lumen ofthe delivery system 1005 as shown in FIG. 34 for delivery of the valve1000 to the left atrium of the heart. As discussed above, by disposingthe outer frame 1020 of the valve 1000 in the inverted configuration,the valve 1000 can be collapsed into a smaller overall diameter, i.e.,placed in a smaller diameter delivery sheath, than would be possible ifthe valve 1000 were collapsed radially when the inner frame 1050 and theouter frame 1020 are disposed concentric to one another.

In this embodiment, the delivery system 1005 includes an outer deliverysheath 1026, an inner sheath 1008, a valve holder 1038 (also referred toas a “pusher”) and a multi-lumen elongate tube member 1003 (alsoreferred to as “tube” or “tube member” or “multi-lumen elongatemember”). As shown in FIGS. 34 and 39-41, the tube member 1003 ismovably disposed within a lumen 1082 defined by the outer deliverysheath 1026. The inner sheath 1008 is movably disposed within the lumen1082 and within a lumen 1080 defined by the tube member 1003. The valveholder 1038 is movably disposed within a first lumen 1083 and a secondlumen 1085 defined by the inner sheath 1008 that are in fluidcommunication with each other.

To deploy the valve 1000 within a heart, the outer frame 1020 of thevalve 1000 is first moved or placed in its inverted configurationrelative to the inner frame 1050. As shown in FIG. 34, a portion of thevalve 1000 is placed within the lumen 1082 of the outer sheath and aportion of the valve 1000 is placed within the lumen 1083 of the innersheath 1008. As described above for previous embodiments, when the valve1000 is placed within the delivery system (e.g., outer sheath 1026 andinner sheath 1008) the valve 1000 can be compressed or collapsed to asmaller configuration (e.g., a smaller outer perimeter).

The inner frame 1050 can be releasably coupled to the valve holder 1038via couplers 1006 that are received within corresponding recesses 1004defined by the valve holder 1038 in the same manner as described abovefor delivery system 405 (see, e.g., FIGS. 26A-26C). In this manner, thevalve holder 1038 can be used to hold the valve 1000 to aid in thecontrol and manipulation of the valve 1000 as it is being deployedwithin a heart. In addition, the valve holder 1038 can limit radialexpansion of the inner frame 1050 as the valve 1000 is moved within thelumen of the delivery sheath 1026 and during deployment outside of thedelivery sheath 1026. As described above for valve 400, an innerdiameter 1082 of the inner sheath 1008 can be sized such that when thevalve holder 1038 and valve 1000 are disposed therein, the couplers 1006are unable to exit the recesses 1004. In other words, the inner walls ofthe inner sheath 1008 maintain the couplers 1006 within the recesses1004. When the valve 1000 is moved outside of the inner sheath 1008, thecouplers 1006 will be able to freely exit the recesses 1004, releasingthe inner frame 1050 from the valve holder 1038.

In alternative embodiments, the valve holder 1038 can be removablycoupled to the valve 1000 (e.g., the inner frame 1050 of the valve 1000)via wires or sutures that can be cut after delivery of the valve 1000 tothe heart. In some cases, the valve holder 1038 can be decoupled fromthe valve 1000 when the valve is still disposed within the outerdelivery sheath 1026, while in other instances the valve holder 1038 canbe decoupled from the valve 1000 after the valve 1000 exits the deliverysheath 1026 within the heart.

Although not shown, in other embodiments, the valve holder 1038 canmerely contact and push the valve 1000 during deployment, as describedfor previous embodiments, without securing the inner frame 1050 to thevalve holder 1038. In such embodiments, in some instances, radialexpansion of the inner frame 1050 can be restricted by the inner sheath1008 when the inner frame 1050 is disposed therein.

In this embodiment a first actuation wire 1076, a second actuation wire1074, a third actuation wire 1076 and a fourth actuation wire 1077 areeach coupled to the outer frame assembly 1010. More specifically, theouter frame 1020 of the outer frame assembly 1010 includes loops 1062through which the actuation wires 1074-1077 can be threaded or receivedtherethrough. In this embodiment, the outer frame 1020 includes 12 loops1062 and each actuation wire 1074-1077 is threaded through 3 of theloops 1062. In other embodiments, there can be a different number ofloops disposed on the outer frame 1020 and there can be a differentnumber of actuators. Further, each actuation wire can be threaded orreceived through a different number of loops than shown for thisembodiment.

When the valve 1000 is disposed within the delivery system 1005 asshown, for example, in FIG. 34, the actuation wires 1074-1077 eachextend from the outer frame 1020 proximally within the lumen 1082 of theouter sheath and along an outside wall of the inner sheath 1008, aretucked or placed behind one or more seals 1081 or other holding device,and pinned by an elongate pinning member 1078-1, 1078-2, 1078-3, 1078-4(collectively referred to as pinning members 1078) to the tube member1003. The seal 1081 can be configured such that the actuation wires1074-1077 can slide relative to the seal 1081 during actuation anddeployment of the valve 1000 as described in more detail below.

As shown in FIGS. 34 and 39-41, a first end of the actuation wire 1074and a first end of the actuation wire 1075 are pinned by a pinningmember 1078-2, and a first end of the actuation wire 1076 and a firstend of the actuation wire 1077 are pinned by a pinning member 1078-1. Asecond end of the actuation wire 1074 and a second end of the actuationwire 1076 are pinned by a pinning member 1078-4 (not shown in thepartial cross-sectional views of FIGS. 34 and 39-41), and a second endof the actuation wire 1075 and a second end of the actuation wire 1077are pinned by a pinning member 1078-3 (not shown in the partialcross-sectional views of FIGS. 34 and 39-41). The second ends of theactuation wires are shown detached in FIGS. 34 and 39-41 for ease ofillustration.

FIG. 35 is a cross-sectional view taken along line 35-35 in FIG. 34 andillustrates the pinning of the actuation wires 1074-1077. The actuationwires 1074-1077 are shown unattached to the outer frame for illustrationpurposes. FIG. 38A illustrates the actuation wire 1074 and isrepresentative of the other actuation wires 1075-1077. FIGS. 38B, 67Band 67C illustrate alternative embodiments for the actuation wireslabeled 1074′, 1074″ and 1074″. As shown in FIG. 38A, the actuationwires 1074-1077 each include a loop on both ends of the actuation wire,which is pinned by the pinning members 1078. In FIG. 38B, the pinningmembers can pin the smaller loop on one end of the actuation wire 1074′and the end of the larger loop on the opposite end of the actuation wire1074′. In FIG. 38C, the actuation wire 2475″ is in the form of a closedloop and each end of the loop can be pinned by a pinning member. In FIG.38D, the actuation wire 1074′″ includes two elongate loops and a centersmaller loop. In this embodiment, the actuation wire 1074′″ can bepinned by three pinning members, a first pinning member can pin an endof one of the larger loops, a second pinning member can pin an end ofthe other larger loop, and the small loop can be pinned by a thirdpinning member. In each of the embodiments of FIGS. 38B-38D, a doublelayer of the actuation wire would be passed or threaded through theloops of the outer frame of the valve. Other alternative configurationscan also be used.

As shown in FIGS. 36 and 37A, the multi-lumen tube member 1003 definesfour pinning member lumens 1079-1, 1079-2, 1079-3, 1079-4 (collectivelyreferred to as pinning member lumens 1079). The end portions of theactuation wires 1074-1077 are placed within the circumferential recessor groove 1084 defined by the tube member 1003, where the pinningmembers 1078 are received through the loops on the ends of the actuationwires 1074-1077, pinning the actuation wires 1074-1077 to the tubemember 1003. Thus, during deployment of the valve 1000 within a heart, auser (e.g., physician) can use the tube member 1003, to which theactuation wires 1074-1077 are coupled, to control and/or manipulatemovement of the valve 1000 as described in more detail below.

FIGS. 37B and 37C, illustrate an alternative embodiment of a multi-lumentube member 1103 that can be used with a distal retention element 1186as shown in FIG. 37B, or a distal retention element 1286 as shown inFIG. 37C. The distal retention elements 1186 and 1286 can be disposedabutting a distal end of the multi-lumen tube member 1103 and can defineat least in part a recess area to receive the loop ends of the actuationwires, and can provide increased overall strength and durability to themulti-lumen tube member 1103 during delivery and deployment of theprosthetic valve. The distal retention element 1186, 1286 can be formedwith the same or a different material as the multi-lumen tube member1103. In some embodiments, in may be desirable for the distal retentionelement 1186, 1286 to be formed of a material having greater strengthcharacteristics than the multi-lumen tube member 1103. For example, thedistal retention element 1186, 1286 can be formed with a metal or rigidplastic.

As shown in FIGS. 37B and 37C, the multi-lumen tube member 1103 (alsoreferred to herein as “tube member”) can define a center lumen 1180 andmultiple pinning member lumens, including pinning member lumens 1179-3and 1179-4 (collectively referred to as 1179) shown in FIGS. 37B and 37Cthat can receive therein pinning members, such as pinning members 1078-3and 1078-4, respectively. Although not show, the tube member 1103 canalso define pinning member lumens that can receive pinning members1078-1 and 1078-2 as shown for tube member 1003 in FIG. 36.

As shown in FIG. 37B, the distal retention element 1186 can be receivedwithin the lumen 1180 and can define a lumen 1187 through which thevalve holder 1038 can be slidably received. Although not shown, thedistal retention element 1186 can be coupled to the tube member 1103using various different coupling methods. For example, in someembodiments, the distal retention element 1186 can be bonded to the tubemember 1103. In some embodiments the distal retention element 1186 caninclude a feature(s), such as barbs, that allow it to be inserted intothe tube member 1103, but not removed. In some embodiments the distalretention element 1186 can include notches that interlock with acorresponding feature o the tube member 1103 and/or the tube member 1103can be reflowed or molded over the retention element 1186. Various othercoupling methods and/or combinations of securement strategies could beused to couple the distal retention element 1186 to the tube member1103. In some embodiments, the distal retention element 1186 can extendproximally within the lumen 1180 of the tube member 1103 and be coupledat a proximal end portion of the tube member 1103.

The distal retention element 1186 also defines pinning member lumens1169 that align with the pinning member lumens 1179 of the multi-lumentube member 1103 such that the pinning members 1078 can be receivedtherein. A proximal shoulder 1188 can be disposed abutting a distal endof the multi-lumen tube member 1103. The distal retention element 1186also defines a circumferential recess area 1184 defined between theproximal shoulder 1188 and a distal end portion of the distal retentionelement 1186. As shown in FIG. 37B, the loop ends of the actuation wires1074-1077 can be received within the recess area 1184 and pinned by thepinning members 1078 as described above for multi-lumen tube member1003.

FIG. 37C illustrates a distal retention element 1286 disposed abuttingthe distal end of the multi-lumen tube member 1103. As with the previousembodiment, the distal retention element 1286 can be received within thelumen 1180 and can define a lumen 1287 through which the valve holder1038 can be slidably received. The distal retention element 1286 can becoupled to the tube member 1103 in the same manner as described abovefor distal retention element 1186. The distal retention element 1286also includes a proximal shoulder 1288 configured to abut the distal endof the multi-lumen tube member 1103. The distal retention element 1286also defines a circumferential recess area 1284 that can receive theloop ends of actuation wires 1074″-1077″, which can be pinned by thepinning members 1078 (1078-3 and 1078-4 shown in FIG. 37C). In thisexample, the actuation wires are configured as a closed loop as shownfor actuation wire 1074″ in FIG. 38C.

The procedure to deliver the valve 1000 to the heart can be the same asor similar to any of the procedures described herein, in '572 PCTApplication and/or the '305 PCT Application incorporated by referenceabove. For example, the valve 1000, disposed within the delivery system1005 in an inverted configuration, can be delivered to the left atriumof the heart in the same or similar manner as described herein withrespect to other embodiments and/or with reference to FIGS. 43-48 of the'305 PCT Application. With the distal end portion of the delivery sheath1026 disposed within the left atrium of the heart, the valve 1000 can bedeployed outside of the delivery sheath 1026. For example, as shown inFIG. 39, the inner sheath 1008, valve holder 1038 and tube member 1003can be moved distally relative to the outer sheath 1026, moving orpushing the valve 1000 outside the lumen 1082 of the outer sheath 1026.In addition, or alternatively, the outer sheath 1026 can be moved orpulled proximally, leaving at least a portion of the valve 1000 disposedwithin the heart. In some cases, the tether 1036 coupled to the valve1000 can be used to help pull the valve 1000 out of the lumen of theouter sheath 1026.

As described above for previous embodiments, as the outer frame 1020becomes unconstrained by the outer sheath 1026, the outer frame 1020 canbegin to revert to its expanded or uninverted configuration. Theactuation wires 1075-1077 can be used to control the reversion of theouter frame 1020. More specifically, the tube member 1003 can be pulledproximally such that the actuation wires (pinned to the tube member1003) pull the distally disposed portion of the outer frame 1020proximally (as shown in FIG. 40) in a controlled manner and such thatthe reversion of the outer frame 1020 from its inverted configurationrelative to the inner frame 1050 can be controlled.

In addition, in some instances, the actuation wires 1074-1077 can assistin the articulation and placement of the valve 1000 into its destination(e.g., a native annulus of an atrioventricular valve of a heart). Forexample, as shown in FIG. 41, the actuation wires 1074-1077 can also beused to constrain, collapse, or otherwise move the valve 1000 (e.g.,radially compress the outer frame 1020 of the valve 1000) after thevalve 1000 exits the outer sheath 1026 and is in its reverted, expandedor partially expanded configuration. More specifically, in thisembodiment, the tube member 1003 with the actuation wires 1074-1077pinned thereto, can be manipulated by a user to move or urge the outerframe to a more compressed configuration (as shown in FIG. 41) bypulling or moving the tube member 1003 proximally. This may bedesirable, for example, to reposition the valve 1000 within the heartbefore fully deploying the valve 1000.

Referring back to FIG. 40, when the outer frame 1020 of the valve 1000is disposed in its non-inverted and at least partially expandedconfiguration, and is in a desired positon within the heart, the innerframe 1050 can be deployed. As described above for valve 400, todecouple the inner frame 1050 from the valve holder 1038, the valveholder 1038 can be moved distally and/or the inner sheath 1008 can bemoved proximally such that the valve holder 1038 is disposed outside ofthe lumen 1083 of the inner sheath 1008. As such, the couplers 1006 canbe released from the recesses 1004 releasing or decoupling the innerframe 1050 from the valve holder 1038. In some embodiments, the tether1036 can be pulled to help move the inner frame 1050 outside of theinner sheath 1008. When the inner frame 1050 is released from the valveholder 1038 and disposed outside the inner sheath 1008, the inner frame1050 can assume its biased expanded configuration.

The actuation wires 1074-1077 can also be released or decoupled from theouter frame 1020 before or after the inner frame 1050 is released formthe valve holder 1038. To decouple the actuation wires 1074-1077 fromthe outer frame 1020, one end of each of the actuation wires 1074-1077can be unpinned or decoupled from the tubular member 1003. For example,as shown in FIG. 42, the pinning member 1078-3 (See FIG. 35) can bewithdrawn proximally from groove 1084 such that the second end of theactuation wire 1077 and the second end of the actuation wire 1075 areeach released or unpinned from the tube member 1003, but remain pinnedby pinning members 1078-2 and 1078-1, respectively. Similarly, thepinning member 1078-4 (see FIG. 35) can be withdrawn proximally fromgroove 1084 such that the second end of the actuation wire 1074 and thesecond end of actuation wire 1076 can each be released or unpinned fromthe tube member 1003, but remain pinned by pinning members 1078-2 and1078-1, respectively. With one end of each of the actuation wires1075-1077 coupled to the tube member 1003 (via pinning members 1078-1and 1078-2 in this example), the tube member 1003 can be pulledproximally, which in turn will pull the opposite ends of the actuationwires 1074-1077 out of the loops 1062 of outer frame 1020. Thus with theactuation wires 1074-1077 detached from the outer frame 1020, the outerframe can assume a biased expanded or partially expanded configuration.

Although in the above example, the pinning members 1078-3 and 1078-4 areshown withdrawn to release the ends of the actuation wires 1074-1077,alternatively, the pinning members 1078-1 and 1078-2 can be withdrawnleaving the actuation wires 1074-1077 pinned by pinning members 1078-3and 1078-4. Further, the actuation wires 1074-1077 can be decoupled fromthe outer frame 1020 at any suitable sequence or time period within theprocedure. For example, in some instances it may be desirable for theactuation wires 1074-1077 to be released after the valve 1000 has atleast partially exited the delivery sheath 1026 but before the valve1000 is seated within the native annulus of the atrioventricular valve.In other instances, for example, the actuation wires 1074-1077 can bereleased after the valve 1000 has at least partially exited the outerdelivery sheath 1026 and after the valve 1000 is seated within thenative annulus of the atrioventricular valve.

FIG. 43 is a flowchart illustrating a method of delivering and deployinga prosthetic valve within a heart. The method includes at 1300,inserting a distal end of a delivery sheath through an apical region ofa heart and into an atrium of the heart. The delivery sheath has aprosthetic heart valve disposed within a lumen of the delivery sheath.The prosthetic heart valve includes an outer frame and an inner framecoupled to the outer frame. The outer frame is movable between a firstposition relative to the inner frame and a second position relative tothe inner frame in which the outer frame is inverted relative to theinner frame. The prosthetic valve is disposed within the lumen of thedelivery sheath with the outer frame in the second position relative tothe inner frame during the inserting. At 1302, the prosthetic heartvalve is moved distally out of the delivery sheath. At 1304, the outerframe of the prosthetic heart valve is transitioned to the firstposition relative to the inner frame such that the prosthetic heartvalve at least partially assumes a biased expanded configuration. At1306, the prosthetic heart valve is positioned within an annulus of theheart.

FIG. 44 is a flowchart illustrating a method of delivering and deployinga prosthetic valve within a heart. At 1400 a distal end portion of adelivery sheath is inserted into an atrium of a heart. The deliverysheath has a prosthetic heart valve disposed within a lumen of thedelivery sheath. The prosthetic heart valve includes an outer frame andan inner frame coupled to the outer frame. The outer frame is movablebetween a first position relative to the inner frame and a secondposition relative to the inner frame in which the outer frame isinverted relative to the inner frame. The prosthetic heart valve isdisposed within the lumen of the delivery sheath with the outer frame inthe second position relative to the inner frame and disposed at leastpartially axially proximal to the inner frame during the inserting. At1402, the prosthetic heart valve is moved distally out of the deliverysheath. At 1404 the outer frame of the prosthetic heart valve istransitioned to the first position relative to the inner frame such thatthe prosthetic heart valve at least partially assumes a biased expandedconfiguration. At 1406, the prosthetic heart valve is positioned withinan annulus of the heart.

While various embodiments have been described above, it should beunderstood that they have been presented by way of example only, and notlimitation. Where methods described above indicate certain eventsoccurring in certain order, the ordering of certain events may bemodified. Additionally, certain of the events may be performedconcurrently in a parallel process when possible, as well as performedsequentially as described above

Where schematics and/or embodiments described above indicate certaincomponents arranged in certain orientations or positions, thearrangement of components may be modified. While the embodiments havebeen particularly shown and described, it will be understood thatvarious changes in form and details may be made. Any portion of theapparatus and/or methods described herein may be combined in anycombination, except mutually exclusive combinations. The embodimentsdescribed herein can include various combinations and/orsub-combinations of the functions, components, and/or features of thedifferent embodiments described.

For example, although not specifically described for each embodiment,any of the embodiments of a delivery system can include a dilator deviceor member such as balloon dilator member. Further, the prosthetic heartvalves described herein can be secured to a heart using an epicardialpad device as described with respect to FIGS. 43-48 and 72 of the '305PCT Application. Moreover, although not shown for each embodiment, anyof the embodiments of a delivery device or system can include a valveholder or valve pusher configured to urge the valve out the distal endof the delivery sheath during delivery of the valve.

Further, although not shown, any of the embodiments of a delivery deviceor system can include a handle or handle assembly to which the variousdelivery sheaths and components can be operatively coupled and which auser (e.g., physician) can grasp and use to manipulate the deliverydevice or system.

In addition, the systems and methods described herein can also beadapted for use with a prosthetic tricuspid valve. For example, in sucha case, a procedural catheter can be inserted into the right ventricleof the heart, and the delivery sheath delivered to the right atrium ofthe heart either directly (transatrial), or via the jugular or femoralvein.

In addition, the systems and methods described herein can also beadapted for use with a prosthetic tricuspid valve. For example, in sucha case, a delivery sheath can be delivered to the heart transapically.

1. A method of delivering a prosthetic heart valve to an annulus of aheart, the method comprising: inserting a distal end portion of adelivery sheath into an atrium of the heart, the delivery sheath havingthe prosthetic heart valve disposed within a lumen of the deliverysheath, the prosthetic heart valve including an outer frame and an innerframe coupled to the outer frame, the outer frame being disposed distalto the inner frame when the prosthetic heart valve is disposed withinthe lumen of the delivery sheath; moving the prosthetic heart valvedistally out of the delivery sheath so that the outer frame beings todeploy from the delivery sheath prior to the inner frame deploying fromthe delivery sheath; causing the outer frame of the prosthetic heartvalve to begin to transition from an inverted position in which theouter frame is disposed distal to the inner frame to a reverted positionin which the outer frame at least partially surrounds the inner frame;and positioning the prosthetic heart valve within the annulus of theheart, wherein as the prosthetic heart valve transitions from theinverted position to the reverted position, couplers of the inner frameare received within recesses of a valve holder within the deliverysheath to prevent the inner frame from moving axially relative to thevalve holder.
 2. The method of claim 1, wherein the couplers of theinner frame are “T”-shaped.
 3. The method of claim 1, furthercomprising: after causing the outer frame of the prosthetic heart valveto begin to transition from the inverted position to the revertedposition, fully deploying the inner frame from the delivery sheath. 4.The method of claim 3, wherein an inner diameter of the delivery sheathis sized such that, when the valve holder and the prosthetic heart valveare disposed therein, the couplers are unable to exit the recesses. 5.The method of claim 4, wherein fully deploying the inner frame from thedelivery sheath includes allowing the couplers to exit the recesses ofthe valve holder when the recesses are positioned distal to the distalend portion of the delivery sheath.
 6. The method of claim 1, wherein aninner sheath is movably positioned within the delivery sheath, and thevalve holder is movably positioned within the inner sheath.
 7. Themethod of claim 1, wherein causing the outer frame of the prostheticheart valve to begin to transition from the inverted position to thereverted position includes pulling an actuation wire coupled to theouter frame in a proximal direction while the couplers of the innerframe are received within the recesses of the valve holder.
 8. Themethod of claim 7, wherein the actuation wire includes a first actuationwire releasably coupled to a first portion of the outer frame, and asecond actuation wire releasably coupled to a second portion the outerframe.
 9. The method of claim 8, wherein the first actuation wire isthreaded circumferentially through a first group of loops on the firstportion of the outer frame, and the second actuation wire is threadedcircumferentially though a second group of loops on the second portionof the outer frame.
 10. The method of claim 7, further comprisingdecoupling the actuation wire from the outer frame after the outer framehas transitioned to the reverted position.
 11. The method of claim 10,wherein decoupling the actuation wire from the outer frame is performedwhile a portion of the prosthetic heart valve is still disposed withinthe delivery sheath.
 12. The method of claim 10, wherein decoupling theactuation wire from the outer frame is performed after the prostheticheart valve is seated within the annulus of the heart.
 13. The method ofclaim 1, wherein inserting the distal end portion of the delivery sheathinto the atrium of the heart include piercing an atrial septum, and theatrium is a left atrium.
 14. The method of claim 13, wherein the annulusof the heart is a mitral valve annulus.
 15. The method of claim 1,wherein inserting the distal end portion of the delivery sheath into theatrium of the heart is performed via a transjugular or transfemoralapproach.
 16. The method of claim 15, wherein the atrium of the heart isa right atrium, and the annulus of the heart is a tricuspid valveannulus.
 17. The method of claim 1, wherein the prosthetic heart valveincludes a tether positioned within a tether coupling portion of theinner frame.
 18. The method of claim 17, further comprising positioningthe tether so that it passes through the annulus of the heart, through aventricle of the heart, and out a puncture site at an apex of the heart.19. The method of claim 18, wherein moving the prosthetic heart valvedistally out of the delivery sheath is performed, at least in part, bypulling on the tether.
 20. The method of claim 18, wherein moving theprosthetic heart valve distally out of the delivery sheath is performed,at least in part, by pushing with the valve holder while pulling on thetether.